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author:("gillberg, Bo")
1.  Genetic Variation in FADS1 Has Little Effect on the Association between Dietary PUFA Intake and Cardiovascular Disease123 
The Journal of Nutrition  2014;144(9):1356-1363.
The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ∆5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ω-3 (n–3) and ω-6 (n–6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA intakes and CVD risk. We included 24,032 participants (62% women, aged 44–74 y) from the Malmö Diet and Cancer cohort without prevalent CVD and diabetes. During a mean follow-up of 14 y, 2648 CVD cases were identified. Diet was assessed by a modified diet history method. A borderline interaction was observed between the α-linolenic acid (ALA) (18:3n–3)-to-linoleic acid (LA) (18:2n–6) intake ratio and FADS1 genotype on CVD incidence (P = 0.06). The ALA-to-LA intake ratio was inversely associated with CVD risk only among participants homozygous for the minor T-allele (HR for quintile 5 vs. quintile 1 = 0.72; 95% CI: 0.50, 1.04; P-trend = 0.049). When excluding participants reporting unstable food habits in the past (35%), the interaction between the ALA-to-LA intake ratio and FADS1 genotype on CVD incidence was strengthened and statistically significant (P = 0.04). Additionally, we observed a significant interaction between ALA and FADS1 genotype on ischemic stroke incidence (P = 0.03). ALA was inversely associated with ischemic stroke only among TT genotype carriers (HR for quintile 5 vs. quintile 1 = 0.50; 95% CI: 0.27, 0.94; P-trend = 0.02). In this large cohort, we found some weak, but not convincing, evidence of effect modification by genetic variation in FADS1 on the associations between PUFA intakes and CVD risk. For the 11% of the population homozygous for the minor T-allele of rs174546 that associates with lower ∆5 FADS activity, high ALA intake and ALA-to-LA intake ratio may be preferable in the prevention of CVD and ischemic stroke.
doi:10.3945/jn.114.192708
PMCID: PMC4130826  PMID: 25008580
2.  A High Diet Quality Is Associated with Lower Incidence of Cardiovascular Events in the Malmö Diet and Cancer Cohort 
PLoS ONE  2013;8(8):e71095.
Aims
To investigate if diet quality is related to incidence of cardiovascular (CV) events.
Subjects and Methods
A diet quality index based on the 2005 Swedish Nutrition Recommendations and the Swedish Dietary Guidelines was created and included six dietary components: saturated fatty acids, polyunsaturated fatty acids, fish and shellfish, dietary fiber, fruit and vegetables, and sucrose. The index ranked 17126 participants (59% women) of the population-based Malmö Diet and Cancer cohort (Sweden) on their dietary intakes. Total index score was categorized as low, medium or high. Cox proportional hazard regression was used to model associations between index score categories and index components with risk of incident CV events, with adjustment for potential confounders. The incidence of first CV events (non-fatal or fatal myocardial infarction or ischemic stroke or death from ischemic heart disease) was monitored from baseline (1991–1996) until December 31, 2008; 703 CV events occurred in women and 1093 in men.
Results
A high diet quality was associated with decreased risk of CV events when compared to a low diet quality. In multivariate analysis, the risk reduction was 32% (hazard ratio = 0.68, 95% confidence interval: 0.49–0.73) in men and 27% (hazard ratio = 0.73, 95% confidence interval: 0.59–0.91) in women. When examined separately and mutually adjusted for each other, the individual components were either not associated with CV risk or marginally decreased risks were seen.
Conclusion
High quality diets in line with current recommendations may reduce the risk of CV events. This study illustrates the importance of considering a combination of dietary factors when evaluating diet-disease associations.
doi:10.1371/journal.pone.0071095
PMCID: PMC3733649  PMID: 23940694
3.  Genetic variation in the fat mass and obesity-associated gene (FTO) in association with food preferences in healthy adults 
Food & Nutrition Research  2013;57:10.3402/fnr.v57i0.20028.
Background
Earlier studies have indicated that the fat mass and obesity-associated gene (FTO) is not only associated with BMI and weight but also with appetite and dietary intake.
Objectives
We investigated if the FTO rs9939609 associates with food preferences in healthy adults with no cancer, cardiovascular disease, or diabetes. Additionally, we challenged the question if the associations are modified by obesity status (BMI ≤25 or >25 kg/m2).
Design
The analyses are made with 22,799 individuals from the Swedish population-based Malmö Diet and Cancer Cohort Study, who were born between 1923 and 1945. To investigate food preference, 27 food groups conducted from a modified diet history method including a 7-day registration of cooked meals and cold beverages were used in the analyses. Bonferroni correction was used to correct for multiple testing, resulting in a cut-off value for significance level of p<0.002.
Results
We observed that the obesity susceptible A-allele carriers reported a higher consumption of biscuits and pastry but lower consumption of soft drinks (P for trend <0.0001 for both) as compared to TT genotype carriers. In contrast to our hypothesis, the results did not significantly differ depending on obesity status except for consumption of juice, where only the overweight individuals with A-allele had a higher consumption as compared to TT carriers (P for interaction=0.04).
Conclusion
Our results indicate that the FTO A-allele may associate with certain food preference and in particular with certain energy-dense foods.
doi:10.3402/fnr.v57i0.20028
PMCID: PMC3625705  PMID: 23589710
obesity; nutrition intake; genetic; Sweden; adults; food preference
4.  Dietary Fiber and Saturated Fat Intake Associations with Cardiovascular Disease Differ by Sex in the Malmö Diet and Cancer Cohort: A Prospective Study 
PLoS ONE  2012;7(2):e31637.
Background
The aim of the study was to examine associations between intake of macronutrients and dietary fiber and incident ischemic cardiovascular disease (iCVD) in men and women.
Methods
We used data from 8,139 male and 12,535 female participants (aged 44–73 y) of the Swedish population-based Malmö Diet and Cancer cohort. The participants were without history of CVD and diabetes mellitus, and had reported stable dietary habits in the study questionnaire. Diet was assessed by a validated modified diet history method, combining a 7-d registration of cooked meals and cold beverages, a 168-item food questionnaire (covering other foods and meal patterns), and a 1-hour diet interview. Sociodemographic and lifestyle data were collected by questionnaire. iCVD cases, which included coronary events (myocardial infarctions or deaths from chronic ischemic heart disease) and ischemic strokes, were ascertained via national and local registries. Nutrient-disease associations were examined by multivariate Cox regressions.
Results
During a mean follow-up of 13.5 years, we identified 1,089 male and 687 female iCVD cases. High fiber intakes were associated with lower incidence rates of iCVD in women and of ischemic stroke in men. In post-hoc analysis, we discovered statistically significant interactions between intake of fiber and saturated fat; these interactions also differed between men and women (p<0.001).
Conclusions
In this well-defined population, a high fiber intake was associated with lower risk of iCVD, but there were no robust associations between other macronutrients and iCVD risk. Judging from this study, gender-specific nutrient analysis may be preferable in epidemiology.
doi:10.1371/journal.pone.0031637
PMCID: PMC3288044  PMID: 22384046
5.  Five meal patterns are differently associated with nutrient intakes, lifestyle factors and energy misreporting in a sub-sample of the Malmö Diet and Cancer cohort 
Food & Nutrition Research  2009;53:10.3402/fnr.v53i0.1970.
Objective
Examine how meal patterns are associated with nutrient intakes, lifestyle and socioeconomic factors, and energy misreporting.
Design
A cross-sectional study within the Malmö Diet and Cancer (MDC) cohort. Participants reported on the overall types and frequency of meals consumed, and completed a modified dietary history, a lifestyle and socioeconomic questionnaire, and anthropometric measurements. Based on the reported intake of six different meal types, meal pattern groups were distinguished using Ward's cluster analysis. Associations between meal patterns and nutrient intakes, anthropometric, lifestyle and socioeconomic variables were examined using the χ2-method and analysis of variance.
Subjects
A sub-sample of the MDC study cohort (n=28,098), consisting of 1,355 men and 1,654 women.
Results
Cluster analysis identified five groups of subjects with different meal patterns in both men and women. These meal pattern groups differed regarding nutrient intakes, lifestyle and socioeconomic factors. Subjects reporting frequent coffee meals were more likely to report an ‘unhealthy’ lifestyle, e.g. smoking, high alcohol consumption and low physical activity, while those with a fruit pattern reported a more ‘healthy’ lifestyle. Women were more likely to underreport their energy intake than men, and the degree of underreporting varied between the meal pattern groups.
Conclusions
The meal pattern groups showed significant differences in dietary quality and socioeconomic and lifestyle variables. This supports previous research suggesting that diet is part of a multifaceted phenomenon. Incorporation of aspects on how foods are combined and eaten into public health advices might improve their efficiency.
doi:10.3402/fnr.v53i0.1970
PMCID: PMC2753298  PMID: 19798420
meal patterns; lifestyle; energy misreporting; cluster analysis
6.  Salivary cortisol differs with age and sex and shows inverse associations with WHR in Swedish women: a cross-sectional study 
Background
Most studies on cortisol have focused on smaller, selected samples. We therefore aimed to sex-specifically study the diurnal cortisol pattern and explore its association with abdominal obesity in a large unselected population.
Methods
In 2001–2004, 1811 men and women (30–75 years) were randomly selected from the Vara population, south-western Sweden (81% participation rate). Of these, 1671 subjects with full information on basal morning and evening salivary cortisol and anthropometric measurements were included in this cross-sectional study. Differences between groups were examined by general linear model and by logistic and linear regression analyses.
Results
Morning and Δ-cortisol (morning – evening cortisol) were significantly higher in women than men. In both genders older age was significantly associated with higher levels of all cortisol measures, however, most consistently with evening cortisol. In women only, age-adjusted means of WHR were significantly lower in the highest compared to the lowest quartile of morning cortisol (p = 0.036) and Δ-cortisol (p < 0.001), respectively. Furthermore, when comparing WHR above and below the mean, the age-adjusted OR in women for the lowest quartile of cortisol compared to the highest was 1.5 (1.0–2.2, p = 0.058) for morning cortisol and 1.9 (1.3–2.8) for Δ-cortisol. All findings for Δ-cortisol remained after adjustments for multiple covariates and were also seen in a linear regression analysis (p = 0.003).
Conclusion
In summary, our findings of generally higher cortisol levels in women than men of all ages are novel and the stronger results seen for Δ-cortisol as opposed to morning cortisol in the association with WHR emphasise the need of studying cortisol variation intra-individually. To our knowledge, the associations in this study have never before been investigated in such a large population sample of both men and women. Our results therefore offer important knowledge on the descriptive characteristics of cortisol in relation to age and gender, and on the impact that associations previously seen between cortisol and abdominal obesity in smaller, selected samples have on a population level.
doi:10.1186/1472-6823-9-16
PMCID: PMC2711063  PMID: 19545400
7.  Diet and body constitution in relation to subgroups of breast cancer defined by tumour grade, proliferation and key cell cycle regulators 
Breast Cancer Research  2007;9(1):R11.
Background
The general lack of clear associations between diet and breast cancer in epidemiological studies may partly be explained by the fact that breast cancer is a heterogeneous disease that may have disparate genetic associations and different aetiological bases.
Method
A total of 346 incident breast cancers in a prospective cohort of 17,035 women enrolled in the Malmö Diet and Cancer study (Sweden) were subcategorized according to conventional pathology parameters, proliferation and expression of key cell cycle regulators. Subcategories were compared with prediagnostic diet and body measurements using analysis of variance.
Results
A large hip circumference and high body mass index were associated with high grade tumours (P = 0.03 and 0.009, respectively), whereas low energy and unadjusted fat intakes were associated with high proliferation (P = 0.03 and 0.004, respectively). Low intakes of saturated, monounsaturated and polyunsaturated fatty acids were also associated with high proliferation (P = 0.02, 0.004 and 0.003, respectively). Low energy and unadjusted fat intakes were associated with cyclin D1 overexpression (P = 0.02 and 0.007, respectively), whereas cyclin E overexpression was positively correlated with fat intake. Oestrogen receptor status and expression of the tumour suppressor gene p27 were not associated with either diet or body constitution.
Conclusion
Low energy and low total fat (polyunsaturated fatty acids in particular) intakes, and high body mass index were associated with relatively more malignant breast tumours. Dietary behaviours and body constitution may be associated with specific types of breast cancer defined by conventional pathology parameters and cyclin D1 and cyclin E expression. Further studies including healthy control individuals are needed to confirm our results.
doi:10.1186/bcr1644
PMCID: PMC1851395  PMID: 17254341
8.  Predictors of acute myocardial infarction mortality in hypertensive patients treated in primary care 
Objective
To explore risk factors for acute myocardial infarction (AMI) mortality in hypertensive patients treated in primary care.
Design
Community-based cohort study.
Setting
Hypertension outpatient clinic in primary health care.
Subjects
Patients who consecutively underwent an annual follow-up during 1992–1993 (n =894; 377 men and 517 women).
Methods
All events of fatal AMI were ascertained by record linkage to the National Mortality Register to December 31, 2002. Gender-specific predictors for AMI mortality were analysed by Cox regression.
Main outcome measure
AMI mortality.
Results
During a mean follow-up of 8.7 years 32 cases (8.5%) of fatal AMI were observed in men and 31 cases (6.0%) were observed in women. Most important predictors for AMI mortality in men were microalbuminuria (HR 3.8, CI 1.8–8.0) and left ventricular hypertrophy (HR 4.0, CI 1.7–9.4), whilst in women type 2 diabetes (HR 4.8, CI 2.4–9.8) was an important predictor. In hypertensive patients without diabetes male gender was associated with high AMI mortality (HR 2.7, CI 1.4–5.3), but in patients with both hypertension and type 2 diabetes the higher risk in men disappeared (HR 0.8, CI 0.4–1.7).
Conclusion
Cardiovascular disease risk factors remain strong predictors of AMI mortality in hypertensive patients but with a different pattern in the two genders. Markers of organ damage are more important predictors in men, whereas markers of impaired glucose metabolism are more important predictors in women.
doi:10.1080/02813430701706253
PMCID: PMC3379766  PMID: 17965983
Acute myocardial infarction; cardiovascular disease risk factors; family practice; hypertension; primary care; type 2 diabetes
9.  A methodological report from the Malmö Diet and Cancer study: development and evaluation of altered routines in dietary data processing 
Nutrition Journal  2002;1:3.
Background
In the Malmö Diet and Cancer study, information on dietary habits was obtained through a modified diet history method, combining a 7-day menu book for cooked meals and a diet questionnaire for foods with low day-to-day variation. Half way through the baseline data collection, a change of interview routines was implemented in order to reduce interview time.
Methods
Changes concentrated on portion-size estimation and recipe coding of mixed dishes reported in the menu book. All method development and tests were carefully monitored, based on experiential knowledge, and supplemented with empirical data. A post hoc evaluation study using "real world" data compared observed means of selected dietary variables before and after the alteration of routines handling dietary data, controlling for potential confounders.
Results
These tests suggested that simplified coding rules and standard portion-sizes could be used on a limited number of foods, without distortions of the group mean nutrient intakes, or the participants' ranking. The post hoc evaluation suggested that mean intakes of energy-adjusted fat were higher after the change in routines. The impact appeared greater in women than in men.
Conclusions
Future descriptive studies should consider selecting subsets assessed with either method version to avoid distortion of observed mean intakes. The impact in analytical studies may be small, because method version and diet assistant explained less than 1 percent of total variation. The distribution of cases and non-cases across method versions should be monitored.
doi:10.1186/1475-2891-1-3
PMCID: PMC149436  PMID: 12537595

Results 1-10 (10)