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author:("Tang, genou")
1.  Genetic and Environmental Contributions to Phenotypic Components of Metabolic Syndrome: A Population-based Twin Study 
Obesity (Silver Spring, Md.)  2009;17(8):1581-1587.
The increasing prevalence of metabolic syndrome (MS) poses a serious public health problem worldwide. Effective prevention and intervention require improved understanding of the factors that contribute to MS. We analyzed data on a large twin cohort to estimate genetic and environmental contributions to MS and to major MS components and their inter-correlations: waist circumference, systolic and diastolic blood pressure, fasting plasma glucose, triglycerides, and high density lipoprotein cholesterol. We applied structural equation modeling to determine genetic and environmental structure of MS and its major components, using 1,617 adult female twin pairs recruited from rural China. The heritability estimate for MS was 0.42 (95% CI: 0.00–0.83) in this sample with low MS prevalence (4.4%). For MS components, heritability estimates were statistically significant and ranged from 0.13 to 0.64 highest for WC, followed by TG, SBP, DBP, HDL-C, and FPG. HDL-C was mainly influenced by common environmental factors (0.62, 95%CI: 0.58–0.62), while the other five MS components were largely influenced by unique environmental factors (0.32–0.44). Bivariate Cholesky decomposition analysis indicated that the clinical clustering of MS components may be explained by shared genetic and/or environmental factors. Our study underscores the importance of examining MS components as inter-correlated traits, and to carefully consider environmental and genetic factors in studying MS etiology.
doi:10.1038/oby.2009.125
PMCID: PMC3766632  PMID: 19407809
metabolic syndrome; twin study; heritability; Chinese
2.  A Common Mutation in DEFB126 Causes Impaired Sperm Function and Subfertility 
Science translational medicine  2011;3(92):92ra65.
A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a 2-nucleotide deletion in the open reading frame, which generates a non-stop mRNA. The allele frequency of this variant sequence is high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from the del/del donors exhibited an 84% reduction in the rate of penetration of a hyaluronic acid (HA) gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in HA gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. However, DEFB126 genotype and lectin binding were highly correlated with performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent cause of impaired reproductive function, provides an opportunity to better understand, clinically evaluate, and possibly treat human infertility.
doi:10.1126/scitranslmed.3002289
PMCID: PMC3736313  PMID: 21775668
3.  Methylenetetrahydrofolate reductase C677T polymorphism is associated with estimated glomerular filtration rate in hypertensive Chinese males 
BMC Medical Genetics  2012;13:74.
Background
Plasma level of total homocysteine (tHcy) is negatively correlated with kidney function in general population. However, the causal mechanism of this correlation is poorly understood. The purpose of this study is to investigate the association of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, which is a major genetic determinant of the plasma tHcy level, with estimated glomerular filtration rate (eGFR) in Chinese.
Methods
A total of 18 814 hypertensive patients (6 914 males, 11 900 females) were included in the study.
Results
Association between the eGFR and MTHFR C677T genotype was examined by sex-specific regression analyses. In males, TT genotype was associated with 1.37 ml/min/1.73 m2 decrease in eGFR (p = 0.004) and with an increased risk (OR = 1.32, p = 0.008) for the lowest quintile of eGFR after adjusting for age, BMI, and blood pressures. However, such association was not observed in females (p > 0.05). This association suggests MTHFR C677T polymorphism may play a role in the regulation of eGFR in males.
Conclusions
MTHFR 677 T is a risk allele for decreased kidney function in Chinese males, implicating this gene in the pathogenesis of chronic kidney disease (CKD).
doi:10.1186/1471-2350-13-74
PMCID: PMC3458982  PMID: 22897803
MTHFR C677T polymorphism; eGFR; CKD
4.  Prevalence and Associated Factors of Diabetes and Impaired Fasting Glucose in Chinese Hypertensive Adults Aged 45 to 75 Years 
PLoS ONE  2012;7(8):e42538.
Objective
This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years.
Methods
A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes.
Results
The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥25kg/m2), abdominal obesity (waist circumference ≥90cm for men and ≥80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG.
Conclusion
In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG evaluation), and treatment of diabetes should be urgently taken to overcome the diabetes epidemic in Chinese hypertensive adults.
doi:10.1371/journal.pone.0042538
PMCID: PMC3411819  PMID: 22880024
5.  Organophosphorous pesticide exposures and sperm quality 
Many Americans are exposed to low levels of organophosphorous (OP) pesticides. In is unclear whether these exposures impact sperm production. We investigated whether there was an association between urinary OP insecticide metabolites and sperm concentration and motility in newly married men from a rural area of eastern People’s Republic of China. Ninety-four cases and 95 controls were included based on their median residual value of sperm concentration and motility after adjusting for relevant covariates. Their urine was analyzed for six dialkylphosphate (DAP) compounds. After adjustment for demographic and exposure variables, the odds of being a case were greater (Odds Ratio=1.30, 95% Confidence Interval 1.02-1.65) in men with higher urinary concentrations of dimethylphosphate (DMP) compared to men with lower levels. No significant differences between cases and controls were found among the other DAP concentrations. DMP exposure and sperm concentration and motility should be explored further in environmental exposure studies.
doi:10.1016/j.reprotox.2010.08.006
PMCID: PMC3035720  PMID: 20850521
Organophosphorous; Insecticides; Pesticides; Reproduction; Semen quality; Hormones; Chinese; Male
6.  Association of central adiposity with pre-diabetes and decreased insulin sensitivity in rural Chinese normal and overweight women 
Objective
This study investigated whether high central adiposity was associated with pre-diabetes and decreased insulin sensitivity (IS) in both normal weight (BMI < 23 kg/m2) and overweight (BMI ≥ 23) rural Chinese women.
Methods
Adipose variables measured by dual energy X-ray absorptiometry (DEXA) (Percent body fat -%BF, percent lower body fat -%LF and percent trunk fat -%TF) and general adipose variables (BMI and waist circumference - WC) were used for examining the association of adiposity with pre-diabetes among 4,071 rural Chinese females aged 20–60 years. Also, the association of adiposity with IS was tested in both normal and overweight women with normal glucose tolerance (NGT).
Results
BMI was highly correlated with %BF and WC, but weakly correlated with %LF and %TF. Both high %TF (top quartile of %TF) and low %LF (lower three quartiles of %LF) were associated with higher prevalence of pre-diabetes in both normal and overweight women. Compared to normal weight women in low %TF, the odds of pre-diabetes were similarly increased for women with high %TF regardless of whether they were overweight (OR (95% CI) = 1.6 (1.3–2.0)) or not (OR (95% CI) = 1.5 (1.2–2.0)). Similarly, among 3,280 women with NGT, high %TF was associated with increased fasting insulin, 2H-OGTT insulin and HOMA-IR regardless of normal or overweight.
Conclusions
Among relatively lean, rural Chinese women, high %TF was associated with increased odds of pre-diabetes and lower IS regardless of normal or overweight.
doi:10.1016/j.metabol.2009.10.029
PMCID: PMC2882526  PMID: 20045140
body fat; adiposity; pre-diabetes; insulin sensitivity; Chinese female
7.  Sleep Patterns Among Rural Chinese Twin Adolescents 
Sleep medicine  2008;10(4):479-489.
Objective
To examine sleep patterns and influencing factors (age, gender, Tanner Stage, weekday vs. weekend, and pre-sleep activity) among rural Chinese adolescents.
Methods
This is a prospective study among 621 adolescents aged 11–20 years (341 males) using both a questionnaire and sleep diary to obtain bedtime, wake-up time, sleep latency, and total sleep time (TST).
Results
The median TST was 8.6 hours on weekdays and 9.4 hours on weekends. Despite absence of late night social pressure and computers, a U-shaped TST pattern was observed across age and Tanner stage, with a nadir around age 15–16 years or Tanner IV. Bedtimes became progressively later with age and Tanner Stage, while wake-up time was considerably earlier for school students or up to Tanner IV. Later wake-up times and longer TST on weekends were seen in school students, but not in non-school adolescents (>17 years). Pre-sleep activity, like reading or studying, was related to later bedtime, earlier wake-up time, and shorter TST in both genders.
Conclusions
Age, Tanner stage, and pre-sleep activity affected sleep patterns in this sample of rural Chinese adolescents. Later bedtime coupled with earlier wake-up time associated with academic demand appear to be important contributors to sleep loss among school students.
doi:10.1016/j.sleep.2008.04.011
PMCID: PMC2753967  PMID: 18752997
Age; gender; puberty; Tanner stages; sleep patterns; wake-up time; bedtime; total sleep time
8.  Ser1369Ala Variant in Sulfonylurea Receptor Gene ABCC8 Is Associated With Antidiabetic Efficacy of Gliclazide in Chinese Type 2 Diabetic Patients  
Diabetes Care  2008;31(10):1939-1944.
OBJECTIVE—The purpose of this study was to investigate whether genetic variants could influence the antidiabetic efficacy of gliclazide in type 2 diabetic patients.
RESEARCH DESIGN AND METHODS—A total of 1,268 type 2 diabetic patients whose diabetes was diagnosed within the past 5 years and who had no recent hypoglycemic treatment were enrolled from 23 hospitals in China. All of the patients were treated with gliclazide for 8 weeks. Fasting and oral glucose tolerance test 2-h plasma glucose, fasting insulin, and A1C were measured at baseline and after 8 weeks of treatment. We used two independent cohorts to test the associations of 25 single nuclear polymorphisms in 11 candidate genes with the antidiabetic efficacy of gliclazide. A general linear regression model was used to test the association with adjustment for important covariates.
RESULTS—After 8 weeks of gliclazide therapy, mean fasting plasma glucose (FPG) was reduced from 11.1 mmol/l at baseline to 7.7 mmol/l. In cohort 1, we genotyped all 25 SNPs (n = 661) and found that Ser1369Ala of the ABCC8 gene and rs5210 of the KCNJ11 gene were significantly associated with decreases in FPG (P = 0.002). We further genotyped Ser1369Ala in cohort 2 (n = 607) and confirmed the association identified in cohort 1. In the pooled analysis, compared with subjects with the Ser/Ser genotype, subjects with the Ala/Ala genotype had a 7.7% greater decrease in FPG (P < 0.001), an 11.9% greater decrease in 2-h plasma glucose (P = 0.003), and a 3.5% greater decrease in A1C (P = 0.06) after 8 weeks of treatment with gliclazide.
CONCLUSIONS—In two independent cohorts of Chinese type 2 diabetic patients, we found consistent evidence that the Ser1369Ala variant in the ABCC8 gene can influence the antidiabetic efficacy of gliclazide.
doi:10.2337/dc07-2248
PMCID: PMC2551631  PMID: 18599530
9.  Association of the Methylenetetrahydrofolate reductase C677T polymorphism and fracture risk in Chinese postmenopausal women* 
Bone  2006;40(3):737-742.
Osteoporotic fractures are a leading cause of disability and, indirectly, of death in the elderly population. Previous studies have shown that homocysteine level and the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) may be involved in the development of osteoporosis and its related fracture in European populations. The aim of this study was to verify the association of this polymorphism with bone mineral density (BMD) and fractures in our 1899 Chinese postmenopausal women. The C677T T-allele frequency in this population was 39.2%. The distribution of the MTHFR genotypes followed the Hardy-Weinberg equilibrium. BMD at total body, total hip or femoral neck did not significantly vary with MTHFR C677T genotype. The T-allele carrier tended to have higher risk of having osteoporosis or osteopenia, but the difference was statistically insignificant. However, Poisson regression analysis revealed that the T-allele carriers had an increased risk of fractures (RR=1.7, 95%CI=1.1–2.7, p=0.01) which occurred before or after menopause. As far as fracture incidence after menopause was concerned, the CT or TT genotype had more than twice the risk of the CC genotype (RR=2.5, 95%CI=1.2–4.9, P=0.009). This association was independent of age, physical activity, occupation, passive smoking, height, weight, years since menopause, and total hip BMD.
Our data show that the MTHFR C677T polymorphism is an independent predictor of fracture risk, although it only had a weak effect on BMD. Further study on the mechanistic role that this polymorphism plays in the development of fractures may lead to better understanding of the etiology of osteoporotic fracture.
doi:10.1016/j.bone.2006.09.031
PMCID: PMC1855293  PMID: 17174622
Methylenetetrahydrofolate Reductase Gene; Fracture; Osteoporosis; Genetics; Postmenopausal Women
10.  Effect of Environmental Tobacco Smoke on Levels of Urinary Hormone Markers 
Environmental Health Perspectives  2005;113(4):412-417.
Our recent study showed a dose–response relationship between environmental tobacco smoke (ETS) and the risk of early pregnancy loss. Smoking is known to affect female reproductive hormones. We explored whether ETS affects reproductive hormone profiles as characterized by urinary pregnanediol-3-glucuronide (PdG) and estrone conjugate (E1C) levels. We prospectively studied 371 healthy newly married nonsmoking women in China who intended to conceive and had stopped contraception. Daily records of vaginal bleeding, active and passive cigarette smoking, and daily first-morning urine specimens were collected for up to 1 year or until a clinical pregnancy was achieved. We determined the day of ovulation for each menstrual cycle. The effects of ETS exposure on daily urinary PdG and E1C levels in a ±10 day window around the day of ovulation were analyzed for conception and nonconception cycles, respectively. Our analysis included 344 nonconception cycles and 329 conception cycles. In nonconception cycles, cycles with ETS exposure had significantly lower urinary E1C levels (β= –0.43, SE = 0.08, p < 0.001 in log scale) compared with the cycles without ETS exposure. There was no significant difference in urinary PdG levels in cycles having ETS exposure (β= –0.07, SE = 0.15, p = 0.637 in log scale) compared with no ETS exposure. Among conception cycles, there were no significant differences in E1C and PdG levels between ETS exposure and nonexposure. In conclusion, ETS exposure was associated with significantly lower urinary E1C levels among nonconception cycles, suggesting that the adverse reproductive effect of ETS may act partly through its antiestrogen effects.
doi:10.1289/ehp.7436
PMCID: PMC1278480  PMID: 15811831
environmental tobacco smoke; estrone conjugates (E1C); pregnanediol-3-glucuronide (PdG); prospective study; urinary hormone levels

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