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1.  High bone turnover elevates the risk of denosumab-induced hypocalcemia in women with postmenopausal osteoporosis 
Hypocalcemia is the most common major adverse event in patients with osteoporosis receiving the bone resorption inhibitor denosumab; however, limited information is available regarding risk factors of hypocalcemia. Therefore, this study aimed to identify the risk factors of hypocalcemia induced by denosumab treatment for osteoporosis. We retrospectively reviewed the records of patients who had received initial denosumab supplemented with activated vitamin D for osteoporosis. Serum levels of the following bone turnover markers (BTMs) were measured at baseline: bone-specific alkaline phosphatase (BAP), total N-terminal propeptide of type 1 procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and urinary cross-linked N-telopeptide of type 1 collagen (NTX). Of the 85 denosumab-treated patients with osteoporosis studied, 22 (25.9%) developed hypocalcemia. Baseline serum total P1NP, TRACP-5b, and urinary NTX were significantly higher in patients with hypocalcemia than in those with normocalcemia following denosumab administration (all P<0.01). Multivariate logistic regression analysis revealed that patients with total P1NP >76.5 μg/L, TRACP-5b >474 mU/dL, or urinary NTX >49.5 nmol bone collagen equivalent/mmol creatinine had a higher risk of hypocalcemia (P<0.01). Our study suggests that denosumab may have a greater impact on serum calcium levels in patients with postmenopausal osteoporosis with higher baseline bone turnover than in patients with postmenopausal osteoporosis with normal baseline bone turnover, because maintenance of normal serum calcium in this subgroup is more dependent on bone resorption. Close monitoring of serum calcium levels is strongly recommended for denosumab-treated patients with high bone turnover, despite supplementation with activated vitamin D and oral calcium.
doi:10.2147/TCRM.S123172
PMCID: PMC5147395  PMID: 27980413
denosumab; hypocalcemia; bone turnover; osteoporosis
2.  Association between distorted body image and changes in weight status among normal weight preadolescents in Japan: a population-based cohort study 
Background
Distorted body image may be important risk factors for being underweight and overweight. The objective of this study was to investigate the association between having a distorted body image and being overweight or underweight among normal weight preadolescents in a population-based cohort study in Japan for each sex.
Methods
The study participants were 1431 normal weight fourth-grade students (age range: 9–10 years) in Ina town, Japan from 2002 to 2007. The height and weight of each student were measured while they were in the fourth grade (at baseline) and seventh grade (3 years later). Childhood underweight and overweight were defined using the body mass index cut-off points proposed by the International Obesity Task Force. Information regarding the self-perceived weight status of each student at baseline was collected using a self-administered questionnaire. Children who were normal weight but perceived themselves as heavy or thin were regarded as having a distorted body images. A logistic regression model was used to calculate the odds ratios (ORs) and 95 % confidence interval (95 % CI) for being overweight or underweight 3 years later among those having a distorted body image at baseline.
Results
Both boys and girls who perceived themselves to be heavy at baseline were at a statistically significantly greater risk of being overweight 3 years later as compared to boys and girls, respectively, who identified as being at a normal weight at baseline (boys: adjusted OR: 4.66, 95 % CI: 1.01–21.48; girls: 3.88, 1.56–9.65). Both boys and girls who perceived oneself to be thin at baseline were at a statistically significantly greater risk of bring underweight 3 years later as compared to boys and girls, respectively, who identified as being at a normal weight at baseline (boys: 5.51, 2.20–13.80; girls: 2.93, 1.40–6.11).
Conclusion
The results of the present study suggest that having a distorted body image in preadolescence is associated with being overweight or underweight in adolescence, among boys and girls, separately. Therefore, education regarding self-perceived weight could be important to help prevent underweight and overweight/obesity among preadolescent boys and girls in Japan.
doi:10.1186/s13690-016-0151-y
PMCID: PMC5028981  PMID: 27660703
Distorted body image; Overweight; Underweight; Preadolescents; Japanese
3.  Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study 
Background
Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.
Methods
A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on elevated levels of serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and serum gamma-glutamyl transpeptidase (GGT) was then conducted.
Results
For men with Mt5178C, after adjustment for age, body mass index, alcohol consumption, habitual smoking, green tea consumption, antihypertensive treatment, and antidiabetic treatment, elevated levels of serum AST, as defined as ≥30 U/L; those of serum ALT, as defined as ≥25 U/L; or those of serum GGT, as defined as ≥60 or >51 U/L, may depend on coffee consumption (P for trend = 0.013, P for trend <0.001, P for trend = 0.002, and P for trend <0.001, respectively). On the other hand, no significant joint effects of Mt5178A genotype and coffee consumption on elevated levels of serum liver enzymes were observed.
Conclusions
The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.
doi:10.1186/s40101-016-0098-2
PMCID: PMC4893217  PMID: 27260124
Coffee consumption; Longevity; Mitochondrial DNA polymorphism; Personalized prevention; Serum liver enzymes
4.  Eating quickly is associated with waist-to-height ratio among Japanese adolescents: a cross-sectional survey 
Background
Central obesity, based on waist circumference (WC), has more adverse effects on health than general obesity, determined by body mass index. To date, eating quickly has been reported to be risk factors for overweight/obesity among children, adolescents, and adults. In contrast, there are few studies on the relationship between fast eating and central obesity among adolescents, particularly in Japan, where WC is not commonly measured in junior high schools. The aim of the present study was to investigate the relationship between eating quickly and waist-to-height ratio (WHtR), an index of central obesity, among adolescents in Japan.
Methods
Study subjects were 2136 seventh-grade school children (12 or 13 years of age) from Ina town junior high schools in Japan, between 2004 and 2009. Measurements of height, weight, and WC were performed, and information about eating habits was collected using a self-administered questionnaire. A logistic regression model was used to calculate the odds ratio (OR) and 95 % confidence interval (95 % CI) for WHtR ≥ 0.5.
Results
Eating quickly significantly increased the OR for WHtR ≥ 0.5 in boys (OR: 2.05, 95 % CI: 1.31–3.23) and girls (2.09, 1.15–3.81). When compared with the “not eating quickly and not eating until full” group, the OR for WHtR ≥ 0.5 in the “eating quickly and eating until full” group was 2.67 (95 % CI: 1.50–4.73) in boys and 2.59 (1.17–5.73) in girls, whereas that in the “eating quickly and not eating until full” group or the “not eating quickly and eating until full” group was not statistically significant regardless of sex.
Conclusions
The present study showed that eating quickly was associated with WHtR ≥ 0.5, and “eating quickly and eating until full” had a substantial impact on WHtR ≥ 0.5 among adolescents. This study suggests that modifying fast eating to a slower pace may help prevent central obesity among adolescents.
doi:10.1186/s13690-016-0130-3
PMCID: PMC4860764  PMID: 27162638
Eating quickly; Waist-to-height ratio; Adolescents; Eating until full
5.  The relationship between distorted body image and lifestyle among Japanese adolescents: a population-based study 
Archives of Public Health  2015;73(1):32.
Background
Distorted body image plays a significant role in the development of obesity, eating problems, and eating disorders. The aim of this study was to investigate the relationship between distorted body image and lifestyle among Japanese adolescent boys and girls.
Methods
Subjects were 1731 seventh graders (age 12–13 years) from the Ina-town’s junior high schools, Japan, from 2005–2009. The height and weight of each subject were measured. Childhood underweight, overweight, and obesity were defined using the body mass index cutoff points proposed by the International Obesity Task Force. Information regarding the self-perceived weight status and lifestyles (exercise, snacking after dinner, breakfast, wakeup time, bedtime) of each subject was collected using a self-administered questionnaire. Self-perceived weight status was categorized into three groups (thin, normal, or heavy), and compared with the subjects’ actual weight status. Body image perception was categorized into the following three groups: an underestimated own weight status group (underestimated group), a correct own weight status group (correct group) and an overestimated own weight status group (overestimated group).
Results
The proportion of boys in the underestimated group was higher than that of girls, while the opposite was true for the overestimated group (P < 0.001). There were no statistically significant differences in lifestyle between the underestimated group and the correct group regardless of sex. In contrast, there were statistically significant differences between the overestimated group and the correct group in the lifestyle factors of exercise among boys and snacking after dinner among girls. The adjusted odds ratio (OR) in boys who exercised daily significantly decreased (OR: 0.35, 95 % CI: 0.16–0.77), while a significantly increased OR was observed in girls who snacked after dinner (OR: 1.53, 95 % CI: 1.07–2.19).
Conclusion
Adolescent boys tended to underestimate their body weight, whereas adolescent girls were likely to overestimate their body weight. Furthermore, lifestyle factors associated with distorted body image differed by sex, with exercise affecting body image perception among boys and snacking after dinner affecting body image perception among girls. Thus, lifestyle may lead to distorted body image among adolescents.
doi:10.1186/s13690-015-0082-z
PMCID: PMC4507316  PMID: 26196011
Distorted body image; Lifestyle; Adolescent; Sex; Japanese
6.  Trends of Underweight and Overweight/Obesity Among Japanese Schoolchildren From 2003 to 2012, Defined by Body Mass Index and Percentage Overweight Cutoffs 
Journal of Epidemiology  2015;25(7):482-488.
Background
We investigated the prevalence and trends of underweight and overweight/obesity in a population-based sample of Japanese schoolchildren from 2003 to 2012, defined by body mass index (BMI) and percentage overweight (POW).
Methods
Subjects comprised fourth and seventh graders from the town of Ina, Japan, from 2003 to 2012. The height and weight of each subject were measured. Children were classified as underweight, normal weight, or overweight/obese using two criteria: BMI cutoff points proposed by the International Obesity Task Force and cutoffs based on POW in Japan.
Results
Data from 4367 fourth graders and 3724 seventh graders were analyzed. The prevalence of underweight and overweight as defined by POW criteria were lower than those based on BMI criteria. There was a decrease in the prevalence of overweight among fourth-grade boys and girls and seventh-grade girls according to BMI; this decrease was also observed when POW criteria were used for the definition of overweight.
Conclusions
The prevalence and trends of both underweight and overweight as defined by POW were underestimated among Japanese schoolchildren compared to those determined using BMI. The results of this study also suggest that trends in underweight and overweight/obesity using POW criteria are similar to those based on BMI criteria among schoolchildren in Japan.
doi:10.2188/jea.JE20140144
PMCID: PMC4483374  PMID: 25986154
body mass index; percentage overweight; schoolchildren; secular trends; Japanese
7.  Waist-to-height ratio is more closely associated with alanine aminotransferase levels than body mass index and waist circumference among population-based children: a cross-sectional study in Japan 
BMC Pediatrics  2015;15:59.
Background
An association between anthropometric measurements, including waist circumference (WC), and alanine aminotransferase (ALT) levels has been reported among adults. However, studies conducted among population-based elementary schoolchildren to date have been limited, especially in Japan, where the measurement of WC and blood collection are not usually performed in the annual health examination at elementary schools. The present study investigated the association between anthropometric measurements and ALT levels among population-based elementary schoolchildren in Japan.
Methods
Subjects were fourth-grade schoolchildren (aged 9 or 10) from the town of Ina in Saitama Prefecture, Japan during 2004–2009. The height, weight, and WC of each subject were measured, and blood samples were drawn to measure ALT levels. Childhood overweight or obesity was defined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman’s correlation coefficients between anthropometric measurements (body mass index (BMI), WC, and waist-to-height ratio (WHtR)) and ALT levels were calculated.
Results
Data from 2499 subjects (1293 boys and 1206 girls) were analyzed. BMI, WC, and WHtR were significantly positively correlated with ALT levels; the correlation coefficient of ALT levels with WHtR was higher than that with BMI and WC in boys and girls. In the analysis stratified by physique (non-overweight/obesity, overweight, or obesity), all anthropometric measurements were significantly positively correlated with ALT levels among boys, while only WHtR was significantly positively correlated with ALT levels among girls. Moreover, the correlation coefficient of ALT levels with WHtR was more pronounced than that with BMI and WC in the non-overweight/obesity group, in the overweight group, and in the obesity group for each sex.
Conclusions
The present study showed that WHtR was more closely associated with ALT levels than BMI and WC. Furthermore, only WHtR was significantly positively associated with ALT levels regardless of sex and physique. This study suggests that it is more useful to monitor WHtR than BMI and WC as a surrogate for ALT levels among population-based elementary schoolchildren.
doi:10.1186/s12887-015-0378-8
PMCID: PMC4477294  PMID: 25980380
Waist-to-height ratio; Alanine aminotransferase; Schoolchildren; Population-based epidemiological study
8.  Association of smoking with intraocular pressure in middle-aged and older Japanese residents 
Objectives
To clarify whether smoking was associated with elevated intraocular pressure (IOP) and to evaluate the interrelationship among IOP, blood viscosity, and smoking.
Methods
This cross-sectional study analyzed health examination data obtained between 2001 and 2004 from 1113 individuals (829 men and 284 women), ranging in age from 28 to 79 years, who had not undergone any ocular surgery or medical treatment for hypertension, ocular hypertension, and glaucoma.
Results
Multiple-regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and number of cigarettes smoked per day had a significantly positive association with IOP in men (P < 0.05). In women also, SBP, DBP, and BMI were positively related to IOP (P < 0.05). On the contrary, age had a significant negative association with IOP in both sexes (P < 0.01). Analysis of covariance and multiple logistic regression analyses showed that the adjusted mean IOP and the multivariate odds ratios for IOP increased with increasing cigarette consumption in men (P for trend = 0.01 and 0.06, respectively). Analysis of covariance found that smoking was significantly associated with both high IOP and high hematocrit in men (P for trend <0.05); however, the adjusted mean IOP values were higher in smokers than in nonsmokers, regardless of the hematocrit level.
Conclusions
The results of this study suggested that the IOP level may be substantially affected by smoking habit in middle-aged and older Japanese men.
doi:10.1007/s12199-013-0359-1
PMCID: PMC3944036  PMID: 23982305
Intraocular pressure; Smoking; Epidemiology; Ocular hypertension; Glaucoma
9.  Longevity-associated mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters in Japanese men: an exploratory cross-sectional analysis 
Background
Mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance. The objective of this analysis was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on erythrocytic parameters in male Japanese health check-up examinees.
Methods
A total of 436 men (mean age ± standard deviation, 54.1 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, an exploratory cross-sectional analysis assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption on red blood cell counts, hematocrit and hemoglobin was conducted.
Results
For Mt5178C genotypic men, after adjustment for age, body mass index, alcohol consumption, habitual smoking and green tea consumption, coffee consumption significantly decreased red blood cell counts (P for trend = 0.022) and hemoglobin (P for trend = 0.035). The risk of anemia, defined as hemoglobin of <14 g/dL, after the aforementioned adjustment, appeared to depend on coffee consumption (P for trend = 0.078), and the adjusted odds ratio for anemia was significantly higher in men who consumed ≥4 cups of coffee per day than in those who consumed <1 cup per day (odds ratio = 3.771, 95% confidence interval: 1.088 to 13.06, P = 0.036). For Mt5178A genotypic men, coffee consumption possibly reduced the risk of anemia (P for trend = 0.049). However, after the aforementioned adjustment, the statistical significance disappeared (P for trend = 0.137).
Conclusions
This exploratory cross-sectional analysis suggests that Mt5178 C/A polymorphism modulates the effects of coffee consumption on erythrocytic parameters and the risk of anemia in male Japanese health check-up examinees.
doi:10.1186/1880-6805-33-37
PMCID: PMC4347656  PMID: 25527868
Anemia; Coffee consumption; Hemoglobin; Mitochondrial DNA polymorphism; Personalized preventive medicine; Red blood cell
10.  NADH dehydrogenase subunit-2 237 Leu/Met polymorphism modifies effects of cigarette smoking on risk of elevated levels of serum liver enzyme in male Japanese health check-up examinees: a cross-sectional study 
Tobacco Induced Diseases  2014;12(1):11.
Background
NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism reportedly influences the effects of cigarette smoking on respiratory function, risk of dyslipidemia, serum non-high-density lipoprotein cholesterol levels, hematological parameters and intraocular pressure. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of cigarette smoking on serum liver enzyme levels in male Japanese health check-up examinees.
Methods
A total of 421 male subjects (mean age ± SD, 54.1 ± 7.7 years) were selected from among individuals visiting the hospital for regular medical check-ups. After ND2-237 Leu/Met genotyping, a cross-sectional study assessing the combined effects of ND2-237 Leu/Met polymorphism and cigarette smoking on serum aspartate aminotransferase levels, serum alanine aminotransferase (ALT) levels and serum gamma-glutamyltransferase (GGT) levels was then conducted.
Results
No statistically significant differences in serum liver enzyme levels among the three smoking status groups (never- or ex-smokers, 1–20 cigarettes smoked per day and >20 cigarettes smoked per day) by ND2-237 Leu/Met genotype were observed. However, for men with ND2-237Met, cigarette smoking significantly increased the risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) (P for trend = 0.031, P for trend = 0.007 and P for trend = 0.004, respectively). After adjustment for age, body mass index, alcohol consumption, coffee consumption, antihypertensive treatment and antidiabetic treatment, a significant association between cigarette smoking and risk of elevated levels of serum ALT (>30 U/L) or serum GGT (≥60 U/L or >51 U/L) was also observed (P for trend = 0.032, P for trend = 0.019 and P for trend = 0.009, respectively). Surprisingly, for men with ND2-237Leu, cigarette smoking significantly decreased the risk of elevated levels of serum ALT (>30 U/L or ≥25 U/L) (P for trend = 0.026 and P for trend = 0.003, respectively).
Conclusions
Cigarette smoking appears to increase the risk of elevated levels of serum ALT or serum GGT in ND2-237Met genotypic men, but to decrease the risk of elevated levels of serum ALT in ND2-237Leu genotypic men.
doi:10.1186/1617-9625-12-11
PMCID: PMC4099487  PMID: 25031572
Alanine aminotransferase; Cigarette smoking; Gamma-glutamyltransferase; Mitochondrial DNA polymorphism; NADH dehydrogenase; Reactive oxygen species
11.  Abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan: a cross-sectional study 
BMC Pediatrics  2014;14:81.
Background
There are a limited number of studies regarding the association between abdominal obesity and serum adiponectin complexes (high, medium, and low molecular weight adiponectins) among population-based elementary school children, especially in Japan, where blood collection is not usually performed during annual health examinations of school children. The aim of the present study was to investigate the relationship between abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan.
Methods
Subjects were all the fourth-grade school children (9 or 10 years of age) in the town of Ina during 2005–2008 (N = 1675). The height, weight, percent body fat, and waist circumference (WC) of each subject were measured. Blood samples were drawn from subjects to measure adiponectin isoform values. Childhood abdominal obesity was defined as “a waist-to-height ratio greater than or equal to 0.5” or “a WC greater than or equal to 75 cm”. The Wilcoxon rank-sum test and the logistic regression model were used to analyze the association between abdominal obesity and each adiponectin isoform value.
Results
Data from 1654 subjects (846 boys and 808 girls) were analyzed. Adiponectin complexes were lower in the abdominal obesity group than in the non-abdominal obesity group regardless of sex. Abdominal obesity significantly increased the odds ratio (OR) for each adiponectin isoform level less than or equal to the median value in boys; the OR (95% confidence interval [CI]) was 2.50 (1.59-3.92) for high molecular weight adiponectin (HMW-adn), 2.47 (1.57-3.88) for medium molecular weight adiponectin (MMW-adn), and 1.75 (1.13-2.70) for low molecular weight adiponectin (LMW-adn). In girls, the OR (95% CI) was 1.95 (1.18-3.21) for HMW-adn, 1.40 (0.86-2.28) for MMW-adn, and 1.06 (0.65-1.70) for LMW-adn.
Conclusions
Abdominal obesity was associated with lower adiponectin complexes and the influence of abdominal obesity varied by adiponectin isoform. Furthermore, the impact of abdominal obesity was larger in boys than in girls. The present study results suggest that prevention of abdominal obesity could contribute to the prevention of lower adiponectin levels, especially in boys.
doi:10.1186/1471-2431-14-81
PMCID: PMC3986877  PMID: 24670108
Abdominal obesity; Serum adiponectin complexes; School children; Population-based epidemiological study
12.  Joint effects of mitochondrial DNA 5178 C/A polymorphism and coffee consumption or alcohol consumption on clustering of cardiovascular risk factors in middle-aged Japanese men: a cross-sectional study 
Background
Longevity-associated mitochondrial DNA 5178 (Mt5178) C/A reportedly modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia and abnormal glucose tolerance, and those of alcohol consumption on the risk of hypertension, dyslipidemia and hyperuricemia in middle-aged Japanese men. However, there has been no research examining whether Mt5178 C/A polymorphism influences the effects of coffee consumption or alcohol consumption on the clustering of cardiovascular risk factors (CRFs).
Methods
A total of 332 male subjects (mean age ± SD, 52.8 ± 7.8 years) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and coffee consumption or alcohol consumption on the clustering of CRFs, namely hypertension, abnormal glucose tolerance, hyper-low-density lipoprotein cholesterolemia, hypo-high density lipoprotein cholesterolemia, hypertriglyceridemia and hyperuricemia, was then conducted.
Results
After adjustment for confounding factors, significant and negative associations were observed between coffee consumption and clustering of ≥2 CRFs in subjects with Mt5178C. The adjusted odds ratio (OR) for the clustering of ≥2 or ≥3 CRFs was significantly lower in subjects who consumed 1–3 cups of coffee per day than in those who consumed <1 cup of coffee per day (OR = 0.496, 95% confidence interval (CI): 0.249–0.989, and OR = 0.369, 95% CI: 0.165–0.826, respectively). On the other hand, after adjustment, positive associations between coffee consumption and clustering of ≥2 CRFs were observed in subjects with Mt5178A. However, these associations did not reach a significant level. For Mt5178C genotypic men, the adjusted OR for the clustering of ≥2 or ≥3 CRFs was significantly higher in daily drinkers than in occasional drinkers (OR = 2.737, 95% CI: 1.361–5.502, and OR = 3.024, 95% CI: 1.269–7.210, respectively). On the other hand, the association between Mt5178A genotype and the clustering of ≥2 or ≥3 CRFs did not appear to depend on alcohol consumption.
Conclusions
The present results suggest that Mt5178 C/A polymorphism modifies the effects of coffee consumption or alcohol consumption on the clustering of CRFs in middle-aged Japanese men.
doi:10.1186/2251-6581-13-4
PMCID: PMC3923557  PMID: 24393210
Alcohol consumption; Cardiovascular risk factor; Coffee consumption; Mitochondrial DNA polymorphism; Personalized prevention
13.  Difference in effects of cigarette smoking or alcohol consumption on serum non-high-density lipoprotein cholesterol levels is related to mitochondrial DNA 5178 C/A polymorphism in middle-aged Japanese men: a cross-sectional study 
Background
Mitochondrial DNA 5178 cytosine/adenosine (Mt5178 C/A) polymorphism is associated with longevity in the Japanese. The purpose of this study is to investigate whether Mt5178 C/A polymorphism modifies the effects of habitual smoking or habitual drinking on serum non-high-density lipoprotein (non-HDL) cholesterol levels in middle-aged Japanese men.
Methods
A total of 394 male subjects (age 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and cigarette smoking or alcohol drinking on serum non-HDL cholesterol levels was conducted. High levels of serum non-HDL cholesterol were defined as serum non-HDL cholesterol levels ≥160 mg/dl or ≥190 mg/dl.
Results
For men with Mt5178A, cigarette smoking may increase serum non-HDL cholesterol levels (P for trend < 0.001), as well as the risk of high levels of non-HDL cholesterol (serum non-HDL cholesterol levels ≥160 mg/dl, P for trend < 0.001; serum non-HDL cholesterol levels ≥190 mg/dl, P for trend = 0.004). On the other hand, for men with Mt5178C, after adjusting for age and body mass index, alcohol consumption may decrease serum non-HDL cholesterol levels (P for trend = 0.043) and the risk of high levels of non-HDL cholesterol (serum non-HDL cholesterol level ≥160 mg/dl, P for trend = 0.005).
Conclusions
These gene-environment interactions on serum non-HDL cholesterol levels may contribute to the establishment of individualized prevention of the risk of high levels of serum non-HDL cholesterol.
doi:10.1186/1880-6805-33-1
PMCID: PMC3905964  PMID: 24383671
Alcohol consumption; Cigarette smoking; Longevity; Mitochondrial DNA polymorphism; Non-HDL cholesterol
14.  Unexpected combined effects of NADH dehydrogenase subunit-2 237 Leu/Met polymorphism and green tea consumption on renal function in male Japanese health check-up examinees: a cross-sectional study 
Background
NADH dehydrogenase subunit-2 237 leucine/methionine (ND2-237 Leu/Met) polymorphism is associated with longevity in Japanese. A previous study has shown that ND2-237 Leu/Met polymorphism modulates the effects of green tea consumption on risk of hypertension. For men with ND2-237Leu, habitual green tea consumption may reduce the risk of hypertension. Moreover, there is a combined effect of ND2-237 Leu/Met polymorphism and alcohol consumption on risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2). Several beneficial effects of green tea on the kidney have been reported. The objective of this study was to investigate whether ND2-237 Leu/Met polymorphism modifies the effects of green tea consumption on risk of mildly decreased eGFR in male Japanese health check-up examinees.
Results
For ND2-237Leu genotypic men, after adjustment for confounding factors, green tea consumption may increase the risk of mildly decreased eGFR (P for trend = 0.016). The adjusted odds ratio (OR) for mildly decreased eGFR was significantly higher in subjects with ND2-237Leu who consume ≥6 cups of green tea per day than those who consume ≤1 cup of green tea per day (adjusted OR = 5.647, 95% confidence interval: 1.528-20.88, P = 0.009). On the other hand, for ND2-237Met genotypic men, green tea consumption does not appear to determine the risk of mildly decreased eGFR.
Conclusion
The present results suggest that ND2-237 Leu/Met polymorphism unexpectedly modifies the effects of green tea consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.
doi:10.1186/1477-5751-12-17
PMCID: PMC3842666  PMID: 24252463
Chronic kidney disease; Estimated glomerular filtration rate; Green tea consumption; NADH dehydrogenase; Polymorphism
15.  Influence of mitochondrial DNA 5178 C/A polymorphism on serum cholesterol changes: a short-term follow-up in middle-aged Japanese men 
Objective
The mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism is reportedly associated with longevity in the Japanese population, and the Mt5178A genotype may exert anti-atherogenic effects. The aim of this study was to determine whether there were longitudinal differences in serum lipid levels between carriers of the Mt5178C genotype and those of the Mt5178A genotype and to assess the impact of these genotypes on serum cholesterol levels.
Methods
The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were measured and the Mt5178 C/A genotypes determined in 110 Japanese men aged 41–66 (mean 52.3) years who had received medical checkups twice in the period 1999–2005. The longitudinal changes of TC, HDLC, and LDLC were calculated according to genotype.
Results
The serum levels of TC at baseline and follow-up were significantly different, whereas those of HDLC and LDLC were not. The changes in HDLC differed significantly between the two Mt5178 C/A genotype groups, with the changes in HDLC level being significantly greater in the Mt5178A genotype group than in the Mt5178C group (p = 0.015).
Conclusions
The Mt5178 C/A genotype may modify longitudinal changes in serum TC and HDLC levels in middle-aged Japanese men.
doi:10.1007/s12199-012-0268-8
PMCID: PMC3437354  PMID: 22351520
Mitochondrial polymorphism; Low-density lipoprotein cholesterol; High-density lipoprotein cholesterol; Follow-up study
16.  Eating Behaviors and Overweight among Adolescents: A Population-Based Survey in Japan 
Journal of Obesity  2013;2013:717942.
Objectives. The aim of the present study was to investigate the relationship between eating behaviors and overweight among population-based adolescents in Japan. Methods. Study subjects comprised adolescents in the seventh grade (age range, 12–13 years) from Ina, a town in Saitama Prefecture, Japan, between 1999 and 2008. The height and weight of the subjects were measured, and information concerning eating behaviors (eating speed and eating until full) was obtained using a self-administered questionnaire. Results. Among boys (n = 1586), fast eating speed significantly increased the odds ratio (OR) for overweight when compared with medium eating speed, regardless of eating until full or not; moreover, a more marked increase in the OR was observed among boys eating until full (OR: 2.78, 95% confidence interval: 1.76–4.38) than among those not eating until full (2.43, 1.41–4.20). Among girls (n = 1542), fast eating speed led to a significant increase in the OR in those eating until full; however, no significant increases were observed in the OR in those eating quickly and not until full. Conclusions. Among adolescents, fast eating speed was associated with overweight; furthermore, the combination of both fast eating speed and eating until full may have a significant effect on overweight.
doi:10.1155/2013/717942
PMCID: PMC3730185  PMID: 23956845
17.  LDL-cholesterol and body mass index among Japanese schoolchildren: a population-based cross-sectional study 
Background
Serum low-density lipoprotein cholesterol (LDL-C) is one of the most important risk factors for coronary heart disease. The aim of the present study was to investigate the relationship between LDL-C and body mass index (BMI) in population-based Japanese schoolchildren.
Methods
The subjects comprised all fourth graders and seventh graders in Ina Town, Saitama Prefecture, Japan, during 2002-2009. Information about each subject’s age, sex, and family history of hypercholesterolemia was collected using a self-administered questionnaire. The body height, weight, and LDL-C were measured for each child. LDL-C was measured using the direct method. According to the LDL-C criteria of the Japan Atherosclerosis Society, LDL-C level was categorized into three subgroups: acceptable, < 110 mg/dL; borderline, 110-139 mg/dL; and high, ≥ 140 mg/dL. Children with either borderline or high LDL-C level were considered to have high-normal LDL-C (HLDL-C).
Results
Data from a total of 5869 subjects were analyzed. A higher BMI category was associated with a higher prevalence of HLDL-C regardless of sex or grade level (P < 0.05). When compared with the <50th percentile BMI category, the odds ratio (OR) for HLDL-C was statistically significant in the 75th to 84th percentile category of fourth-grade boys (OR: 1.95, 95% confidence interval (95% CI): 1.28-2.97), the 85th to 94th percentile of fourth-grade girls (2.52, 1.74-3.64), and the 85th to 94th percentile of seventh-grade boys (2.04, 1.31-3.20) and girls (1.90, 1.24-2.91).
Conclusion
A statistically significant association between LDL-C levels and BMI was observed in Japanese school children.
doi:10.1186/1476-511X-12-77
PMCID: PMC3680021  PMID: 23705977
Serum low-density lipoprotein; Body mass index; Schoolchildren
18.  Combined effect of mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on estimated glomerular filtration rate in male Japanese health check-up examinees: a cross-sectional study 
BMC Nephrology  2013;14:35.
Background
Prevention of chronic kidney disease (CKD) is a major public health issue. Although several studies have been performed on the association between alcohol consumption and CKD or renal function, it remains controversial. Numerous genetic polymorphisms have been reported to be associated with CKD and kidney function. Mitochondrial DNA cytosine/adenine (Mt5178 C/A) polymorphism is associated with longevity in Japanese. This polymorphism modifies the effects of alcohol consumption on blood pressure, risk of hypertension, serum triglyceride levels, risk of hyper-LDL cholesterolemia and serum uric acid levels. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of alcohol consumption on renal function in male Japanese health check-up examinees.
Methods
A total of 394 male subjects aged 29–76 years were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effects of Mt5178 C/A polymorphism and habitual drinking on the risk of mildly decreased estimated glomerular filtration rate (eGFR) (<90 ml/min/1.73 m2) was conducted.
Results
For Mt5178A genotypic men, habitual drinking may increase eGFR (P for trend = 0.003) or reduce the risk of mildly decreased eGFR (P for trend = 0.003). Daily drinkers had a significantly higher eGFR than non-drinkers (P = 0.005). The crude odds ratio for decreased eGFR was significantly lower in daily drinkers than in non-drinkers (odds ratio = 0.092, 95% confidence interval: 0.012-0.727, P = 0.024). On the other hand, for Mt5178C genotypic men, habitual drinking does not appear to affect eGFR.
Conclusion
The present results suggest a joint effect of Mt5178 C/A polymorphism and alcohol consumption on eGFR and the risk of mildly decreased eGFR in male Japanese subjects.
doi:10.1186/1471-2369-14-35
PMCID: PMC3575228  PMID: 23402433
Alcohol; Chronic kidney disease; Estimated glomerular filtration rate; Mitochondrial DNA polymorphism
19.  Childhood Mortality Due to Unintentional Injuries in Japan, 2000–2009 
This study examined deaths due to unintentional injuries among children in Japan to identify the age groups and sexes at most risk, and the types of injuries, so that effective forms of targeted intervention can be devised. Among children aged 0–14 years, deaths whose underlying causes had been classified under code V01-X59 of the ICD-10 were defined as deaths of children caused by unintentional injuries. Using data from the Vital Statistics 2000–2009 for analysis, we examined the changes in mortality and trends in terms of sex, age, and cause of death. Mortality decreased by 46.2%, from 933 in 2000 to 502 in 2009. The mortality rate among children aged 1–4 years decreased by almost half. The total number of deaths during this decade was 7,362 (boys: 4,690, girls: 2,672). Among the causes of death, the majority were due to “transport accidents”, followed by “other accidental threats to breathing”, and “accidental drowning and submersion”. The characteristics observed in terms of sex, age, and cause of death—that is, deaths from suffocation among infants aged less than 1 year, drowning deaths among boys, and transport accidents involving pedestrians and cyclists—must be addressed as targets for future intervention.
doi:10.3390/ijerph10020528
PMCID: PMC3635160  PMID: 23364538
unintentional injury; childhood mortality; cause of death; Japan
20.  Number of siblings, birth order, and childhood overweight: a population-based cross-sectional study in Japan 
BMC Public Health  2012;12:766.
Background
Although several studies have investigated the relationship between the number of siblings or birth order and childhood overweight, the results are inconsistent. In addition, little is known about the impact of having older or younger siblings on overweight among elementary schoolchildren. The present population-based study investigated the relationship of the number of siblings and birth order with childhood overweight and evaluated the impact of having younger or older siblings on childhood overweight among elementary schoolchildren in Japan.
Methods
Subjects comprised fourth-grade schoolchildren (age, 9–10 years) in Ina Town during 1999–2009. Information about subjects’ sex, age, birth weight, birth order, number of siblings, lifestyle, and parents’ age, height, and weight was collected by a self-administered questionnaire, while measurements of subjects’ height and weight were done at school. Childhood overweight was defined according to age- and sex-specific cut-off points proposed by the International Obesity Task Force. A logistic regression model was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI) of "number of siblings" or "birth order" for overweight.
Results
Data from 4026 children were analyzed. Only children (OR: 2.13, 95% CI: 1.45-3.14) and youngest children (1.56, 1.13-2.16) significantly increased ORs for overweight compared with middle children. A larger number of siblings decreased the OR for overweight (P for trend < 0.001). Although there was no statistically significant relationship between a larger number of older siblings and overweight, a larger number of younger siblings resulted in a lower OR for overweight (P for trend < 0.001).
Conclusions
Being an only or youngest child was associated with childhood overweight, and having a larger number of younger siblings was negatively associated with overweight. The present study suggests that public health interventions to prevent childhood overweight need to focus on children from these family backgrounds.
doi:10.1186/1471-2458-12-766
PMCID: PMC3509397  PMID: 22966779
Sibling; Birth-order; Childhood overweight; Public health
21.  High-molecular-weight adiponectin and anthropometric variables among elementary schoolchildren: a population-based cross-sectional study in Japan 
BMC Pediatrics  2012;12:139.
Background
Studies about the relationship between high-molecular-weight adiponectin (HMW-adn) and anthropometric variables among population-based elementary schoolchildren have been too limited, especially in Japan, where blood collection is not usually performed in the annual health examination at elementary schools. The objective of the present study was to investigate the relationship between HMW-adn and anthropometric variables (body mass index [BMI], percent body fat [%BF], waist circumference [WC], and waist-to-height ratio [WHtR]) among population-based elementary schoolchildren in Japan.
Methods
Subjects comprised all fourth-grade schoolchildren (9 or 10 years of age) in the town of Ina, Saitama Prefecture, Japan during 2005–2008 (N = 1675). After excluding 21 subjects because of refusal to participate or incomplete data, data from a total of 1654 subjects (846 boys and 808 girls) were analyzed. The height, weight, %BF, and WC of each subject were measured, while blood samples were drawn from the subjects to measure adiponectin levels (HMW-adn and total adiponectin). Childhood obesity was determined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman’s correlation coefficients between adiponectin levels and anthropometric variables were calculated for each sex.
Results
The anthropometric variables were negatively correlated with HMW-adn in both boys and girls. Correlation coefficients of HMW-adn with anthropometric variables in the obesity group were consistently higher than those in the non-obesity group among both boys and girls. In addition, only WHtR was significantly correlated with HMW-adn regardless of sex and physique (obesity or non-obesity); the correlation coefficient was -0.386 among boys and -0.543 among girls in the obesity group, while it was -0.124 among boys and -0.081 among girls in the non-obesity group.
Conclusions
HMW-adn was negatively correlated with anthropometric variables, while the correlation coefficients of HMW-adn with anthropometric variables in the obesity group were consistently higher than those in the non-obesity group. Moreover, only WHtR was significantly associated with HMW-adn regardless of sex and physique. The results of this study suggested that it is useful to monitor WHtR as a surrogate for HMW-adn among elementary school students, especially obese children.
doi:10.1186/1471-2431-12-139
PMCID: PMC3478987  PMID: 22937905
High-molecular-weight adiponectin; Anthropometric variable; Obesity; Waist-to-height ratio; Children
22.  Mitochondrial DNA 5178 C/A polymorphism influences the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men 
Background
Several genetic polymorphisms have been reported to modify the effects of smoking on serum lipid levels. The objective of this study was to investigate whether longevity-associated mitochondrial DNA 5178 (Mt5178) C/A polymorphism modifies the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese subjects.
Methods
A total of 394 male subjects (age, 53.9 ± 7.9 years; mean ± SD) were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effect of Mt5178 C/A polymorphism and cigarette smoking on the risk of hypo-high-density lipoprotein (HDL) cholesterolemia, hyper-low-density lipoprotein (LDL) cholesterolemia or hypertriglyceridemia was conducted.
Results
For subjects with Mt5178C, the risk of hypo-HDL cholesterolemia increased with the number of cigarettes smoked daily (P for trend = 0.001). On the other hand, the association between Mt5178A genotype and the risk of hypo-HDL cholesterolemia did not appear to depend on the number of cigarettes smoked daily. For those with Mt5178A, the risk of hyper-LDL cholesterolemia or hypertriglyceridemia increased with cigarettes smoked daily (P for trend = 0.017 and P for trend = 0.002, respectively). However, the association between Mt5178C genotype and the risk of hyper-LDL cholesterolemia or hypertriglyceridemia did not depend on the number of cigarettes smoked daily.
Conclusions
The present results suggest that Mt5178 C/A polymorphism modulates the effects of habitual smoking on the risk of dyslipidemia in middle-aged Japanese men.
doi:10.1186/1476-511X-11-97
PMCID: PMC3459723  PMID: 22857129
Cigarette smoking; Hypo-HDL cholesterolemia; Hyper-LDL cholesterolemia; Hypertriglyceridemia; Mitochondrial DNA polymorphism; Personalized preventive medicine
23.  Eating Behavior and Childhood Overweight Among Population-Based Elementary Schoolchildren in Japan  
This study investigated the relationship between eating behavior and childhood overweight among population-based elementary schoolchildren in Japan. Data was collected from fourth graders (9 or 10 years of age) from Ina Town, Saitama Prefecture, Japan from 1999 to 2009. Information about subjects’ sex, age, and lifestyle, including eating behaviors (eating until full and chewing thoroughly), was obtained using a self-administered questionnaire, and height and weight were measured directly. Overweight was determined according to the definition established by the International Obesity Task Force. Data from 4027 subjects (2079 boys and 1948 girls) were analyzed. Chewing thoroughly was associated with a significantly decreased odds ratio (OR) for being overweight, whereas eating until full significantly increased the OR for being overweight (OR: 1.50, 95% confidence interval: 1.16–1.94) among boys. However, eating until full was not associated with a significantly increased OR for being overweight among the group that reported chewing thoroughly, whereas it was associated with a significantly increased OR for being overweight (2.02, 1.38–2.94) among boys who did not chew thoroughly. In conclusion, eating until full or not chewing thoroughly was associated with being overweight among elementary schoolchildren. Results of this study suggest that chewing thoroughly may be an avenue to explore childhood overweight prevention efforts.
doi:10.3390/ijerph9041398
PMCID: PMC3366619  PMID: 22690201
eating behavior; overweight; children; eating until full; chewing
24.  Joint effect of longevity-associated mitochondrial DNA 5178 C/A polymorphism and alcohol consumption on risk of hyper-LDL cholesterolemia in middle-aged Japanese men 
Background
Combined effects between mitochondrial DNA 5178 (Mt5178) C/A polymorphism and alcohol consumption on the risk of hypertension or hyperuricemia have been reported. The objective of this study was to investigate whether Mt5178 C/A polymorphism modulates the effects of alcohol consumption on the risk of dyslipidemia.
Methods
A total of 394 male subjects were selected from among individuals visiting the hospital for regular medical check-ups. After Mt5178 C/A genotyping, a cross-sectional study assessing the combined effect of Mt5178 polymorphism and alcohol consumption on the risk of dyslipidemia was conducted.
Results
For men with Mt5178C, alcohol consumption was significantly and negatively associated with the risk of hyper-low-density lipoprotein (LDL) cholesterolemia (serum LDL cholesterol ≥ 140 mg/dl) (P for trend = 0.015). After adjustment for age, body mass index (BMI), habitual smoking, coffee consumption and use of antihypertensive medicine, the odds ratio (OR) for hyper-LDL cholesterolemia was significantly lower in daily drinkers with Mt5178C than non-drinkers with Mt5178C (OR = 0.360, 95% confidence intervals: 0.153-0.847). A significant and negative association between alcohol consumption and serum LDL cholesterol levels was also observed in Mt5178C genotypic men (P for trend < 0.01). On the other hand, the association between Mt5178A genotype and risk of hyper-LDL cholesterolemia does not appear to depend on alcohol consumption.
Conclusions
For Mt5178C genotypic men, alcohol consumption may reduce the risk of hyper-LDL cholesterolemia.
doi:10.1186/1476-511X-10-105
PMCID: PMC3134423  PMID: 21702983
25.  High Blood Pressure in Obese and Nonobese Japanese Children: Blood Pressure Measurement is Necessary Even in Nonobese Japanese Children 
Journal of Epidemiology  2010;20(5):408-412.
Background
Although the prevalences of obesity and hypertension (HT) are increasing in children, there have been few epidemiological studies of HT in Japanese children. We evaluated the prevalences of HT and high-normal blood pressure (HNBP), and examined the relationship between blood pressure (BP) and body mass index (BMI), in Japanese children.
Methods
The subjects of this study were 2420 children living in the town of Ina, Saitama Prefecture, Japan during the period from 2006 through 2008. Body height, weight, and BP were measured. HT and HNBP were defined according to the HT criteria for Japanese children. Children with HNBP or HT were defined as having high blood pressure (HBP).
Results
The prevalences of HBP were 15.9% and 15.8% in fourth-grade boys and girls, respectively, and 11.1% and 10.8% in seventh-grade boys and girls, respectively. Irrespective of sex or grade level, a higher BMI was associated with a higher prevalence of HBP (P < 0.001). When compared with the <50th percentile BMI category, the crude odds ratios (ORs) were statistically significant for the 75th to 84th percentile category in fourth-grade boys (OR: 4.54, 95% CI: 2.36–8.76), the ≥95th percentile in fourth-grade girls (13.29, 5.93–29.77), the 85th to 94th percentile (3.16, 1.46–6.84) in seventh-grade boys, and the ≥95th percentile (7.96, 3.18–19.93) in seventh-grade girls.
Conclusions
BMI was associated with HBP in Japanese school children. In addition, some children in the lower BMI categories also had HBP.
doi:10.2188/jea.JE20090207
PMCID: PMC3900836  PMID: 20699600
high blood pressure; children; BMI; hypertensive family history

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