Substitution of pure fruit juice for fruit and sugar-sweetened beverages and cardiometabolic risk in European Prospective Investigation into Cancer and Nutrition (EPIC)-NL: a prospective cohort study.

OBJECTIVE: Dietary guidelines on pure fruit juice differ between countries regarding the question whether pure fruit juice (without added sugars) is an acceptable substitute for fruit or should be avoided because of its comparable sugar content with that of sugar-sweetened beverages (SSB). We modelled whether substituting pure fruit juice for fruit or SSB was associated with cardiometabolic risk. DESIGN: Prospective cohort study. SETTING: Based on a validated FFQ at baseline, we calculated the relative contribution of pure fruit juice to total consumption of fruit and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{fruit}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$) and to total consumption of SSB and pure fruit juice (${{{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\;\left( {{\rm{g}}/{\rm{day}}} \right)} \over {{\rm{SSBs}}\; + \;{\rm{pure}}\;{\rm{fruit}}\;{\rm{juice}}\;\left( {{\rm{g}}/{\rm{day}}} \right)}}$). In multivariate analyses (Cox regression), we assessed associations with incidence of type 2 diabetes, CVD, CHD and stroke after an average follow-up of 14·6 years. PARTICIPANTS: About 35 000 participants from the EPIC-NL study, aged 20-70 years at enrolment. RESULTS: Substitution of pure fruit juice for SSB was associated with lower risk of all endpoints. For type 2 diabetes and CHD, for example, drinking 75-100 % (as compared with 0-<25 %) of total SSB + pure fruit juice as pure fruit juice showed hazard ratio (95 % CI) of 0·74 (95 % CI 0·64, 0·85) and 0·85 (95 % CI 0·76, 0·96), respectively. Substitution of pure fruit juice for fruit was not associated with the risk of type 2 diabetes, CVD, CHD and stroke. CONCLUSIONS: Substituting pure fruit juice for SSB was associated with lower cardiometabolic risk, whereas substituting pure fruit juice for fruit was not associated with cardiometabolic risk.

Limited effect of duration of CMV infection on adaptive immunity and frailty: insights from a 27-year-long longitudinal study.

OBJECTIVES: Cytomegalovirus infection is thought to affect the immune system and to impact general health during ageing. Higher CMV-specific antibody levels in the elderly are generally assumed to reflect experienced viral reactivation during life. Furthermore, high levels of terminally differentiated and CMV-specific T cells are hallmarks of CMV infection, which are thought to expand over time, a process also referred to as memory inflation. METHODS: We studied CMV-specific antibody levels over ~ 27 years in 268 individuals (aged 60-89 years at study endpoint), and to link duration of CMV infection to T-cell numbers, CMV-specific T-cell functions, frailty and cardiovascular disease at study endpoint. RESULTS: In our study, 136/268 individuals were long-term CMV seropositive and 19 seroconverted during follow-up (seroconversion rate: 0.56%/year). CMV-specific antibody levels increased slightly over time. However, we did not find an association between duration of CMV infection and CMV-specific antibody levels at study endpoint. No clear association between duration of CMV infection and the size and function of the memory T-cell pool was observed. Elevated CMV-specific antibody levels were associated with the prevalence of cardiovascular disease but not with frailty. Age at CMV seroconversion was positively associated with CMV-specific antibody levels, memory CD4+ T-cell numbers and frailty. CONCLUSION: Cytomegalovirus-specific memory T cells develop shortly after CMV seroconversion but do not seem to further increase over time. Age-related effects other than duration of CMV infection seem to contribute to CMV-induced changes in the immune system. Although CMV-specific immunity is not evidently linked to frailty, it tends to associate with higher prevalence of cardiovascular disease.

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women.

Anti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in MCM8 has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10 -8 : the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 , and CDCA7 . The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (r g = 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the AMH gene and three other loci that may affect circulating AMH levels in women.

Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality: EPIC cohort study in 10 European countries.

OBJECTIVE: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN: Population based cohort study. SETTING: European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS: 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE: Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS: After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P<0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P<0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P<0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS: In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.

Are our diets getting healthier and more sustainable? Insights from the European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) cohort.

OBJECTIVE: To identify differences in dietary quality, dietary greenhouse gas (GHG) emissions and food consumption over 20 years in a Dutch cohort. DESIGN: Participants (n 8932) filled out an FFQ in 1993-1997 and in 2015. The Dutch Healthy Diet index 2015 (DHD15-index) score, GHG emissions and consumption of food groups (g/4184 kJ (1000 kcal)) were compared between the time points with paired t tests. SETTING: The Netherlands. PARTICIPANTS: European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) cohort, aged 18-65 years at baseline. RESULTS: Total energy intake decreased by -678 (95 % CI -4908, 3377) kJ/d (-162 (95 % CI -1173, 807) kcal/d) for men and -372 (95 % CI -3820, 3130) kJ/d (-89 (95 % CI -913, 748) kcal/d) for women. DHD15-index scores increased by 11 % (from 64·8 to 71·9 points) and 13 % (from 65·2 to 73·6 points) in men and women, respectively (P < 0·0001), mainly due to an increased (shell)fish and nuts/seeds/nut paste consumption. After energy intake adjustment, dietary-related GHG emissions increased by 5 % in men (2·48-2·61 kg CO2-eq/4184 kJ (1000 kcal), P < 0·0001) and were similar in women (0·4 %, 2·70-2·71 kg CO2-eq/4184 kJ (1000 kcal), P = 0·3930) due to the increased consumption of (shell)fish, nuts/seeds/nut paste, poultry and higher GHG-intensive red meats such as beef. CONCLUSIONS: This Dutch cohort analyses showed more healthy diets without mitigated GHG emissions over a 20-year period, at similar energy intakes. Higher consumption of (shell)fish and poultry was not yet at the expense of red and processed meat. Lower consumption of animal-based foods is needed to achieve healthier as well as environmentally friendly diets.

A new selection method to increase the health benefits of CVD prevention strategies.

Background Cardiovascular disease (CVD) prevention is commonly focused on providing individuals at high predicted CVD risk with preventive medication. Whereas CVD risk increases rapidly with age, current risk-based selection of individuals mainly targets the elderly. However, the lifelong (preventable) consequences of CVD events may be larger in younger individuals. The purpose of this paper is to investigate if health benefits from preventive treatment may increase when the selection strategy is further optimised. Methods Data from three Dutch cohorts were combined ( n = 47469, men:women 1:1.92) and classified into subgroups based on age and gender. The Framingham global risk score was used to estimate 10-year CVD risk. The associated lifelong burden of CVD events according to this 10-year CVD risk was expressed as quality-adjusted life years lost. Based on this approach, the additional health benefits from preventive treatment, reducing this 10-year CVD risk, from selecting individuals based on their expected CVD burden rather than their expected CVD risk were estimated. These benefits were expressed as quality-adjusted life years gained over lifetime. Results When using the current selection strategy (10% risk threshold), 32% of the individuals were selected for preventive treatment. When the same proportion was selected based on burden, more younger and fewer older individuals would receive treatment. Across all individuals, the gain in quality-adjusted life years was 217 between the two strategies, over a 10-year time horizon. In addition, when combining the strategies 5% extra eligible individuals were selected resulting in a gain of 628 quality-adjusted life years. Conclusion Improvement of the selection approach of individuals can help to reduce further the CVD burden. Selecting individuals for preventive treatment based on their expected CVD burden will provide more younger and fewer older individuals with treatment, and will reduce the overall CVD burden.

Association of dietary protein and dairy intakes and change in renal function: results from the population-based longitudinal Doetinchem cohort study.

BACKGROUND: Evidence has suggested that protein from dairy may be less detrimental to renal health than protein from nondairy products. However, to our knowledge, no previous studies have used cystatin C-based measures of the estimated glomerular filtration rate (eGFR). OBJECTIVE: We investigated the associations of sources of protein and dairy with the change in the eGFR in persons with a normal or mildly decreased eGFR. DESIGN: We included 3798 participants, aged 26-65 y, from the Doetinchem Cohort study who were examined ≥3 times 5 y apart. Intakes of protein and dairy and subtypes of protein and dairy were assessed at each round. With the use of the Chronic Kidney Disease Epidemiology Collaboration equation, the eGFR was estimated from cystatin C with all available samples per participant examined in one assay run. Generalized estimating equation models, which were adjusted for lifestyle, biological, and other dietary factors (monounsaturated fat, polyunsaturated fat, phosphorus, magnesium, calcium, and vitamin D) were performed. RESULTS: The mean baseline eGFR in the total cohort and in subjects with a mildly decreased eGFR (≥1 eGFR of 60-90 mL · min-1 · 1.73 m-2 during follow-up; n = 1326) was 108.6 and 95.2 mL · min-1 · 1.73 m-2, and the mean annual decline in both groups was 1.01 and 1.34 mL · min-1 · 1.73 m-2, respectively. Intakes of total, vegetable, animal, and nondairy protein, dairy protein, cheese, total dairy, high-fat dairy, and fermented dairy were not associated with eGFR changes. In individuals with a mildly decreased eGFR, higher consumption of milk, milk products, and low-fat dairy was associated with less annual decline in the eGFR (P-trend = 0.003). These associations were partially explained by dietary components of dairy (monounsaturated fat, polyunsaturated fat, phosphorus, magnesium, calcium, and vitamin D; P-trend < 0.04). CONCLUSIONS: Higher low-fat dairy consumption, but not sources of protein, is associated with less annual decline in the eGFR, particularly in individuals with a mildly decreased eGFR. These associations are partly attributable to other major components of dairy. Confirmation of these results will improve our ability to understand the role of dairy consumption in the prevention of renal dysfunction.

Shift workers have a similar diet quality but higher energy intake than day workers.

OBJECTIVE: Shift work is associated with adverse health outcomes, and an unhealthy diet may be a contributing factor. We compared diet quantity and quality between day and shift workers, and studied exposure-response relationships regarding frequency of night shifts and years of shift work. METHODS: Cross-sectional general population data from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort was used. Dietary intake was assessed in 1993-1997 among adults aged 20-70 years using a food frequency questionnaire. We calculated energy intake, the Mediterranean Diet Score (MDS) and WHO-based Healthy Diet Indicator (HDI). In 2011-2014, we retrospectively identified 683 shift workers and 7173 day workers in 1993-1997. Using multivariable-adjusted linear regression analysis, we estimated regression coefficients (ß) and 95% confidence intervals (95% CI) of the differences in dietary intake between day and shift workers. RESULTS: Shift workers had a higher energy intake than day workers (ß:56 kcal/d, 95% CI 10-101), and a higher consumption of grains, dairy products, meat and fish (P<0.05). The difference in energy intake was largest for shift workers with ≥5 night shifts/month. They consumed 103 kcal/d (95% CI 29-176) more than day workers. No associations were found with MDS and HDI. CONCLUSION: Shift workers and particularly those with a high frequency of night shifts had a higher energy intake than day workers. Regardless of number of night shifts and years of shift work, shift workers had similar diet quality as day workers. This suggests that increased energy intake among shift workers may contribute to shift work-induced adverse health outcomes.

Coffee and tea consumption in relation to estimated glomerular filtration rate: results from the population-based longitudinal Doetinchem Cohort Study.

BACKGROUND: Although coffee consumption and tea consumption have been linked to diabetes, the relation with kidney function is less clear and is underresearched. OBJECTIVE: We investigated the prospective associations of coffee and tea consumption with estimated glomerular filtration rate (eGFR). DESIGN: We included 4722 participants aged 26-65 y from the Doetinchem Cohort Study who were examined every 5 y for 15 y. Coffee and tea consumption (in cups/d) were assessed at each round. eGFR was assessed by using the Chronic Kidney Disease Epidemiology Collaboration equation based on both plasma creatinine and cystatin C. We determined the association between categories of coffee and tea intake and 1) eGFR and 2) subsequent annual changes in eGFR by using generalized estimating equation analyses. RESULTS: Baseline mean ± SD eGFR was 108.0 ± 14.7 mL · min(-1) · 1.73 m(-2) Tea consumption was not associated with eGFR. Those individuals who drank >6 cups coffee/d had a 1.33 (95% CI: 0.24, 2.43) mL · min(-1) · 1.73 m(-2) higher eGFR than those who drank <1 cup/d (P-trend = 0.02). This association was most apparent among those with a median age of ≥46 y at baseline, with eGFR being 2.47 (95% CI: 0.42, 4.51) mL · min(-1) · 1.73 m(-2) higher in participants drinking >6 cups/d compared with <1 cup/d (P-trend = 0.02). Adjustment for biological risk factors and coffee constituents did not attenuate the associations. Neither coffee nor tea consumption was associated with changes in eGFR. CONCLUSIONS: Coffee consumption was associated with a slightly higher eGFR, particularly in those aged ≥46 y. The absence of an association with eGFR changes suggests that the higher eGFR among coffee consumers is unlikely to be a result of glomerular hyperfiltration. Therefore, low to moderate coffee consumption is not expected to be a concern for kidney health in the general population.

Reducing our environmental footprint and improving our health: greenhouse gas emission and land use of usual diet and mortality in EPIC-NL: a prospective cohort study.

BACKGROUND: Food choices influence health status, but also have a great impact on the environment. The production of animal-derived foods has a high environmental burden, whereas the burden of refined carbohydrates, vegetables and fruit is low. The aim of this study was to investigate the associations of greenhouse gas emission (GHGE) and land use of usual diet with mortality risk, and to estimate the effect of a modelled meat substitution scenario on health and the environment. METHODS: The usual diet of 40011 subjects in the EPIC-NL cohort was assessed using a food frequency questionnaire. GHGE and land use of food products were based on life cycle analysis. Cox proportional hazard ratios (HR) were calculated to determine relative mortality risk. In the modelled meat-substitution scenario, one-third (35 gram) of the usual daily meat intake (105 gram) was substituted by other foods. RESULTS: During a follow-up of 15.9 years, 2563 deaths were registered. GHGE and land use of the usual diet were not associated with all-cause or with cause-specific mortality. Highest vs. lowest quartile of GHGE and land use adjusted hazard ratios for all-cause mortality were respectively 1.00 (95% CI: 0.86-1.17) and 1.05 (95% CI: 0.89-1.23). Modelled substitution of 35 g/d of meat with vegetables, fruit-nuts-seeds, pasta-rice-couscous, or fish significantly increased survival rates (6-19%), reduced GHGE (4-11%), and land use (10-12%). CONCLUSIONS: There were no significant associations observed between dietary-derived GHGE and land use and mortality in this Dutch cohort. However, the scenario-study showed that substitution of meat with other major food groups was associated with a lower mortality risk and a reduced environmental burden. Especially when vegetables, fruit-nuts-seeds, fish, or pasta-rice-couscous replaced meat.

Effect of including nonfatal events in cardiovascular risk estimation, illustrated with data from The Netherlands.

AIMS: European physicians use SCORE risk charts to predict a patient's 10-year risk of cardiovascular diseases (CVD) mortality. We examined whether the inclusion of nonfatal events improved risk estimation and the identification of high-risk persons. METHODS AND RESULTS: In the EPIC-NL cohort, risk factor data were collected between 1993 and 1997 in 6772 men and 9108 women aged 35-65 years. During 10 years of follow up, 540 total (fatal + nonfatal) CVD events occurred, of which 122 (23%) were fatal. Risk equations were developed using Cox proportional hazard models. Discriminating ability and hazard ratios for CVD risk factors did not differ between the two endpoints. Absolute risks for total CVD were approximately 4-fold higher than for CVD mortality. Using the current 5% CVD mortality threshold or the 22% total CVD threshold for identification of high-risk persons leaves more than 84% of all male and 98% of all female future cases untreated. Of those exceeding these thresholds, 20% and 27% of the men, respectively, and 16% and 19% of women will get a CVD event in the next 10 years. Cut-off points of 2% for CVD mortality, corresponding to 10% for total CVD, will identify high-risk persons of whom approximately 10% will get an event in the next 10 years. CONCLUSION: CVD mortality comprises a quarter of all total CVD events. Risk functions and the discriminating ability did not differ between the two endpoints. Cut-off points of 2% for CVD mortality or 10% for total CVD could be considered to identify high-risk persons.

An overview of the European Health Examination Survey Pilot Joint Action.

BACKGROUND: Health Examination Surveys (HESs) can provide essential information on the health and health determinants of a population, which is not available from other data sources. Nevertheless, only some European countries have systems of national HESs. A study conducted in 2006-2008 concluded that it is feasible to organize national HESs using standardized measurement procedures in nearly all EU countries. The feasibility study also outlined a structure for a European Health Examination Survey (EHES), which is a collaboration to organize standardized HESs in countries across Europe.To facilitate setting up national surveys and to gain experience in applying the EHES methods in different cultures, EHES Joint Action (2010-2011) planned and piloted standardized HESs in the working age population in 12 countries. This included countries with earlier national HESs and countries which were planning their first national HES. The core measurements included in all surveys were weight, height, waist circumference and blood pressure, and blood samples were taken to measure lipid profiles and glucose or glycated haemoglobin (HbA1c). These are modifiable determinants of major chronic diseases not identified in health interview surveys. There was a questionnaire to complement the data on the examination measurements. METHODS: Evaluation of the pilot surveys was based on review of national manuals and evaluation reports of survey organizers; observations and discussions of survey procedures during site visits and training seminars; and other communication with the survey organizers. RESULTS: Despite unavoidable differences in the ways HESs are organized in the various countries, high quality and comparability of the data seems achievable. The biggest challenge in each country was obtaining high participation rate. Most of the pilot countries are now ready to start their full-size national HES, and six of them have already started. CONCLUSIONS: The EHES Pilot Project has set up the structure for obtaining comparable high quality health indicators on health and important modifiable risk factors of major non-communicable diseases from the European countries. The European Union is now in a key position to make this structure sustainable. The EHES core survey can be expanded to cover other measurements.

Efficacy of multifactorial lifestyle interventions in patients with established cardiovascular diseases and high risk groups.

BACKGROUND: Lifestyle modification is recommended for patients with established cardiovascular diseases (CVD) or at high risk of CVD. In recent years, risk factor interventions in which multiple risk factors are addressed simultaneously are increasingly conducted. AIM: To determine, and if possible quantify, the efficacy of multifactorial lifestyle interventions (without drug therapy) in patients with established CVD or in high risk groups. METHODS: A literature search was conducted using 'Pubmed', to identify articles of randomized controlled trials (RCTs) or reviews of RCTs, published between 1990 and 2007. RESULTS: In patients with established CVD, multifactorial lifestyle interventions can reduce the occurrence of cardiovascular diseases and/or mortality, even many years after the end of the intervention. Further, in both patients and high risk groups, multifactorial lifestyle interventions have favorable effects on biological risk factors and lifestyle and are able to reduce the incidence of diabetes. In the long-term, in particular lifestyle changes seem to persist, such as improved dietary habits and increased physical activity, while the favorable effects on biological risk factors, such as body weight and blood pressure, are no longer different from the control group. Regular contact with the participants seems to be part of the "success factor". CONCLUSION: It can be recommended to offer patients with established CVD as well as individuals at high risk of CVD a comprehensive lifestyle advice, as part of their medical treatment, combined with intensive counseling.

Five-year effect of community-based intervention Hartslag Limburg on quality of life: a longitudinal cohort study.

BACKGROUND: During the past decade, quality of life (QoL) has become an accepted measure of disease impact, therapeutic outcome, and evaluation of interventions. So far, very little is known about the effects of community-based interventions on people's QoL. Therefore, the effect of an integrative cardiovascular diseases community-based intervention programme 'Hartslag Limburg' on QoL after 5-years of intervention is studied. METHODS: A longitudinal cohort study comparing 5-year mean change in QoL between the intervention (n = 2356) and reference group (n = 758). QoL outcomes were the physical and mental health composite scores (PCS and MCS) measured by the RAND-36. Analyses were stratified for gender and socio-economic status (SES). RESULTS: After 5-years of intervention we found no difference in mean change in PCS and MCS between the intervention and reference group in both genders and low-SES. However, for the moderate/high SES intervention group, the scales social functioning (-3.6, 95% CI:-6.1 to -1.2), physical role limitations (-5.3, 95% CI:-9.6 to -1.0), general mental health (-3.0, 95% CI:-4.7 to -1.3), vitality (-3.2, 95% CI:-5.1 to -1.3), and MCS (-1.8, 95% CI:-2.9 to -0.6) significantly changed compared with the reference group. These differences were due to a slight decrease of QoL in the intervention group and an increase of QoL in the reference group. CONCLUSION: Hartslag Limburg has no beneficial effect on people's physical and mental QoL after 5-years of intervention. In fact, subjects in the intervention group with a moderate/high SES, show a decrease on their mental QoL compared with the reference group.

Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study.

BACKGROUND: The delta-5 and delta-6 desaturases, encoded by the FADS1 and FADS2 genes, are rate-limiting enzymes in polyunsaturated fatty acid (PUFA) biosynthesis. Single nucleotide polymorphisms in the FADS gene cluster region have been associated with both PUFA concentrations in plasma or erythrocyte membrane phospholipids and cholesterol concentrations in recent genome-wide association studies. OBJECTIVE: We examined whether genetic variations in the FADS gene cluster region interact with dietary intakes of n-3 (omega-3) and n-6 (omega-6) PUFAs to affect plasma total, HDL-, and non-HDL-cholesterol concentrations. DESIGN: Dietary intakes of n-3 and n-6 PUFAs, plasma concentrations of total and HDL cholesterol, and rs174546, rs482548, and rs174570 in the FADS gene cluster region were measured in 3575 subjects in the second survey of the Doetinchem Cohort Study. RESULTS: Significant associations between rs174546 genotypes and total and non-HDL-cholesterol concentrations were observed in the group with a high intake of n-3 PUFAs (> or =0.51% of total energy; P = 0.006 and 0.047, respectively) but not in the low-intake group (P for interaction = 0.32 and 0.51, respectively). The C allele was associated with high total and non-HDL-cholesterol concentrations. Furthermore, the C allele was significantly associated with high HDL-cholesterol concentrations in the group with a high intake of n-6 PUFAs (> or =5.26% of total energy, P = 0.004) but not in the group with a low intake (P for interaction = 0.02). CONCLUSION: Genetic variation in the FADS1 gene potentially interacts with dietary PUFA intakes to affect plasma cholesterol concentrations, which should be investigated further in other studies.