Associations between dietary patterns and gene expression profiles of healthy men and women: a cross-sectional study.

BACKGROUND: Diet regulates gene expression profiles by several mechanisms. The objective of this study was to examine gene expression in relation with dietary patterns. METHODS: Two hundred and fifty four participants from the greater Quebec City metropolitan area were recruited. Two hundred and ten participants completed the study protocol. Dietary patterns were derived from a food frequency questionnaire (FFQ) by factor analysis. For 30 participants (in fasting state), RNA was extracted from peripheral blood mononuclear cells (PBMCs) and expression levels of 47,231 mRNA transcripts were assessed using the Illumina Human-6 v3 Expression BeadChips®. Microarray data was pre-processed with Flexarray software and analysed with Ingenuity Pathway Analysis (IPA). RESULTS: Two dietary patterns were identified. The Prudent dietary pattern was characterised by high intakes of vegetables, fruits, whole grain products and low intakes of refined grain products and the Western dietary pattern, by high intakes of refined grain products, desserts, sweets and processed meats. When individuals with high scores for the Prudent dietary pattern where compared to individuals with low scores, 2,083 transcripts were differentially expressed in men, 1,136 transcripts in women and 59 transcripts were overlapping in men and women. For the Western dietary pattern, 1,021 transcripts were differentially expressed in men with high versus low scores, 1,163 transcripts in women and 23 transcripts were overlapping in men and women. IPA reveals that genes differentially expressed for both patterns were present in networks related to the immune and/or inflammatory response, cancer and cardiovascular diseases. CONCLUSION: Gene expression profiles were different according to dietary patterns, which probably modulate the risk of chronic diseases. TRIAL REGISTRATION: NCT: NCT01343342.

Omega-3 fatty acids status in human subjects estimated using a food frequency questionnaire and plasma phospholipids levels.

BACKGROUND: Intakes of omega-3 (n-3) fatty acids (FA) are associated with several health benefits. The aim of this study was to verify whether intakes of n-3 FA estimated from a food frequency questionnaire (FFQ) correlate with n-3 FA levels measured in plasma phospholipids (PL). METHODS: The study sample consisted of 200 French-Canadians men and women aged between 18 to 55 years. Dietary data were collected using a validated FFQ. Fasting blood samples were collected and the plasma PL FA profile was measured by gas chromatography. RESULTS: Low intakes of n-3 long-chain FA together with low percentages of n-3 long-chain FA in plasma PL were found in French-Canadian population. Daily intakes of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were similar between men and women. Yet, alpha-linolenic acid (ALA) and total n-3 FA intakes were significantly higher in men compared to women (ALA: 2.28 g and 1.69 g, p < 0.0001, total n-3 FA: 2.57 g and 1.99 g, p < 0.0001; respectively). In plasma PL, DPA and DHA percentages were significantly different between men and women (DPA: 1.03% and 0.88%, p < 0.0001, DHA: 3.00% and 3.43%, p = 0.0005; respectively). Moreover, DHA (men: r = 0.52, p < 0.0001; women: r = 0.57, p < 0.0001) and total n-3 FA (men: r = 0.47, p < 0.0001; women: r = 0.52, p < 0.0001) intakes were positively correlated to their respective plasma PL FA levels. In women, EPA (r = 0.44, p < 0.0001) and DPA (r = 0.23, p = 0.02) intakes were also correlated respectively with EPA and DPA plasma PL FA percentages. CONCLUSION: Estimated n-3 long-chain FA intake among this young and well-educated French-Canadian population is lower than the recommendations. Further, FFQ data is comparable to plasma PL results to estimate DHA and total n-3 FA status in healthy individuals as well as to evaluate the EPA and DPA status in women. Overall, this FFQ could be used as a simple, low-cost tool in future studies to rank n-3 FA status of individuals.

Associations between dietary patterns and LDL peak particle diameter: a cross-sectional study.

OBJECTIVE: Dietary patterns are used to evaluate the effects of overall nutritional habits on health status, and low-density lipoprotein-peak particle diameter (LDL-PPD) has been recognized as an emerging risk factor for cardiovascular disease (CVD). The aim of this study is to verify whether an association exists between dietary patterns and LDL-PPD. METHODS: A total of 635 participants aged between 18 and 55 years were included in this cross-sectional study. Nutritional information was collected with a validated food frequency questionnaire. To establish dietary patterns, factor analysis was performed, which led to characterization of the Western and Prudent dietary patterns. Nondenaturing 2%-16% polyacrylamide gradient gel electrophoresis was used to characterize LDL-PPD. RESULTS: The Western pattern was characterized by high consumption of food such as refined grains, French fries, and red meats, and the Prudent pattern by nonhydrogenated fat, vegetables, eggs, and fish. For the Western profile, a negative correlation was found between score value and LDL-PPD before (r = -0.082, p = 0.039) and after adjustment for age (r = -0.080, p = 0.043). A negative correlation between scores for the Prudent profile and the LDL-PPD adjusted for age, sex, plasma triglycerides, and energy was observed (r = -0.12204, p = 0.0021). After division by tertiles and adjustment for the confounding effects of age, sex, plasma triglyceride levels, and energy, a significant difference (p = 0.0015) in LDL-PPD was noted between the highest tertile (255.21 ± 3.61 Å) and the lowest tertile (255.79 ± 3.68 Å) of the Prudent pattern. CONCLUSIONS: Dietary patterns, such as the Western and the Prudent, are associated with LDL-PPD. Dietary patterns can be used to assess the effects of nutritional habits on health status.

Eating behaviours of non-obese individuals with and without familial history of obesity.

The aim of the present study was to examine whether eating behaviours and their subscales are associated with familial history of obesity (FHO) in a cohort of 326 non-obese men and women. Anthropometric measurements, eating behaviours (Three-Factor Eating Questionnaire) and dietary intakes (FFQ) have been determined in a sample of 197 women and 129 men. A positive FHO (FHO+) was defined as having at least one obese first-degree relative and a negative FHO (FHO-) as no obese first-degree relative. Men with FHO+ had higher scores of cognitive dietary restraint and flexible restraint than men with FHO-. In women, those with FHO+ had a higher score of disinhibition than women with FHO-. In both men and women, eating behaviours were not significantly associated with the number of obese family members. However, having an obese mother was associated with higher scores of cognitive dietary restraint, flexible restraint and rigid restraint in women. These findings demonstrate that eating behaviours of non-obese subjects are different according to the presence or absence of obese family members. More specifically, having an obese mother is associated with a higher dietary restraint score in women.

Validity of a self-reported measure of familial history of obesity.

BACKGROUND: Familial history information could be useful in clinical practice. However, little is known about the accuracy of self-reported familial history, particularly self-reported familial history of obesity (FHO). METHODS: Two cross-sectional studies were conducted. The aims of study 1 was to compare self-reported and objectively measured weight and height whereas the aims of study 2 were to examine the relationship between the weight and height estimations reported by the study participants and the values provided by their family members as well as the validity of a self-reported measure of FHO. Study 1 was conducted between 2004 and 2006 among 617 subjects and study 2 was conducted in 2006 among 78 participants. RESULTS: In both studies, weight and height reported by the participants were significantly correlated with their measured values (study 1: r = 0.98 and 0.98; study 2: r = 0.99 and 0.97 respectively; p < 0.0001). Estimates of weight and height for family members provided by the study participants were strongly correlated with values reported by each family member (r = 0.96 and 0.95, respectively; p < 0.0001). Substantial agreement between the FHO reported by the participants and the one obtained by calculating the BMI of each family members was observed (kappa = 0.72; p < 0.0001). Sensitivity (90.5%), specificity (82.6%), positive (82.6%) and negative (90.5%) predictive values of FHO were very good. CONCLUSION: A self-reported measure of FHO is valid, suggesting that individuals are able to detect the presence or the absence of obesity in their first-degree family members.

A simple method to assess fruit and vegetable intake among obese and non-obese individuals.

OBJECTIVES: Fruit and vegetable (F&V) consumption is generally associated with the prevention of major chronic diseases. For monitoring purposes, public health researchers require short but reliable and valid questionnaires to assess F&V consumption. The aim of the present study was to validate a brief one-page self-administered fruit and vegetable questionnaire (FV-Q) for obese and non-obese populations. METHODS: The validation study was conducted from 2004 to 2006, among a sample of 350 obese and non-obese French-speaking participants. The six-item FV-Q was designed to measure F&V consumption over a seven-day period. It was validated against an interviewer-administered Food Frequency Questionnaire (FFQ) by means of correlation analysis and computing of epidemiologic indices. The analyses were performed separately for obese and non-obese individuals in order to account for potential different reporting patterns and the absence of such validation in obese populations. All the analyses were performed during 2007. RESULTS: For obese and non-obese participants, the Pearson correlation coefficients between the FV-Q and FFQ were, respectively, r = 0.66 (p<0.0001) and r=0.65 (p<0.0001) for the mean daily intake. Values for sensitivity and specificity were 88.5% and 63.6% for obese individuals and 80.0% and 65.6% for non-obese individuals, respectively. Positive predictive values were moderate in both groups, whereas negative predictive values were very good. Overall, results were very similar for obese and non-obese individuals. CONCLUSIONS: This brief F&V questionnaire can be used to identify people requiring nutritional counseling. Moreover, it can be used for both obese and non-obese populations.

Dietary intakes and familial history of obesity.

PURPOSE: To compare dietary intakes of individuals with and without familial history of obesity (FHO) with recommendations from Canada's Food Guide to Healthy Eating (CFGHE). METHODS: This cross-sectional study recruited 197 women and 129 men with a body mass index of less than 30kg/m(2) from the Quebec City metropolitan area. A dietitian obtained their dietary intakes, using a food frequency questionnaire. RESULTS: Daily energy, macronutrient, and fibre intakes were not significantly different between individuals with and without FHO. No significant differences in the proportion of individuals who achieved the minimum CFGHE recommendations were observed between individuals with and without FHO. CONCLUSIONS: Findings of our study suggest that individuals with and without FHO have comparable dietary intakes when compared to Canadian dietary guidelines.

Dietary patterns and associated lifestyles in individuals with and without familial history of obesity: a cross-sectional study.

BACKGROUND: Familial history of obesity (FHO) and certain dietary habits are risk factors for obesity. The objectives of this cross-sectional study were 1) to derive dietary patterns using factor analysis in a population of men and women with and without FHO; 2) to compare mean factor scores for each dietary pattern between individuals with and without FHO; and 3) to examine the association between these patterns and anthropometric, lifestyle and sociodemographic variables. METHODS: A total of 197 women and 129 men with a body mass index <30 kg/m2 were recruited. A positive FHO (FHO+) was defined as having at least one obese first-degree relative and a negative FHO (FHO-) as no obese first-degree relative. Dietary data were collected from a food frequency questionnaire. Factor analysis was performed to derive dietary patterns. Mean factor scores were compared using general linear model among men and women according to FHO. Regression analyses were performed to study the relationship between anthropometric, lifestyle and sociodemographic variables, and each dietary pattern. RESULTS: Two dietary patterns were identified in both men and women : the Western pattern characterized by a higher consumption of red meats, poultry, processed meats, refined grains as well as desserts, and the Prudent pattern characterized by greater intakes of vegetables, fruits, non-hydrogenated fat, and fish and seafood. Similar Western and Prudent factor scores were observed in individual with and without FHO. In men with FHO+, the Western pattern is negatively associated with age and positively associated with physical activity, smoking, and personal income. In women with FHO-, the Prudent pattern is negatively associated with BMI and smoking and these pattern is positively associated with age and physical activity. CONCLUSION: Two dietary patterns have been identified among men and women with and without FHO. Although that FHO does not seem to influence the adherence to dietary patterns, results of this study suggest that anthropometric, lifestyle and sociodemographic variables associated with dietary patterns differ according to FHO and gender.

The peroxisome proliferator-activated receptor alpha Leu162Val polymorphism influences the metabolic response to a dietary intervention altering fatty acid proportions in healthy men.

BACKGROUND: Serum lipid responses to dietary modification are partly determined by genetic factors. OBJECTIVE: We tested whether plasma lipoprotein and lipid responsiveness to a modification in the dietary ratio of polyunsaturated to saturated fatty acids (P:S) is influenced by the peroxisome proliferator-activated receptor alpha (PPARalpha) Leu162Val polymorphism in healthy men. DESIGN: Ten carriers of the V162 allele and 10 L162 homozygotes were matched according to age and body mass index (BMI). During the protocol, all subjects followed the National Cholesterol Education Program Step I diet, but intake of saturated and polyunsaturated fatty acids was adjusted to obtain a P:S of 0.3 for the first 4-wk period (low-P:S diet) and a P:S of 1.0 for the next 4-wk period (high-P:S diet). RESULTS: At screening, the PPARalpha Leu162Val polymorphism was not associated with anthropometric indexes or plasma lipoprotein and lipid concentrations. After the high-P:S diet, a significant gene-by-diet interaction was observed for changes in plasma total cholesterol, apolipoprotein (apo) A-I, and cholesterol concentrations in small LDL particles (P

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population.

OMIC technologies, including transcriptomics and metabolomics, may provide powerful tools for identifying the effects of nutrients on molecular functions and metabolic pathways. The objective was to investigate molecular and metabolic changes following n-3 polyunsaturated fatty acid (PUFA) supplementation in healthy subjects via traditional biomarkers as well as transcriptome and metabolome analyses. Thirteen men and 17 women followed a 2-week run-in period based on Canada's Food Guide and then underwent 6-week supplementation with n-3 PUFA (3 g/day). Traditional biochemical markers such as plasma lipids, inflammatory markers, glycemic parameters and erythrocyte fatty acid concentrations were measured. Changes in gene expression of peripheral blood mononuclear cells were assessed by microarrays, and metabolome profiles were assessed by mass spectrometry assay kit. After supplementation, plasma triglycerides decreased and erythrocyte n-3 PUFA concentrations increased to a similar extent in both genders. Further, plasma high-density lipoprotein cholesterol concentrations and fasting glucose levels increased in women after n-3 PUFA supplementation. N-3 PUFA supplementation changed the expression of 610 genes in men, whereas the expression of 250 genes was altered in women. Pathway analyses indicate changes in gene expression of the nuclear receptor peroxisome proliferator-activated receptor-alpha, nuclear transcription-factor kappaB, oxidative stress and activation of the oxidative stress response mediated by nuclear factor (erythroid-derived 2)-like 2. After n-3 PUFA supplementation, metabolomics profiles demonstrate an increase in acylcarnitines, hexose and leucine in men only and a decrease in saturation of glycerophosphatidylcholine and lysophosphatidylcholine concentrations in all subjects. Overall, traditional and novel biomarkers suggest that n-3 PUFA supplementation exerts cardioprotective effects.

Association between plasma omega-3 fatty acids and cardiovascular disease risk factors.

The consumption of omega-3 (n-3) fatty acids (FA), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been linked to reduced cardiovascular disease (CVD) risk. The objective of this study was to examine the relation between n-3 FA in plasma phospholipid (PL) levels and CVD risk factors. n-3 FA levels in plasma PL were determined using gas chromatography in 100 obese (body mass index (BMI), ≥30 kg·m(-2)) and 100 nonobese selected individuals from the Quebec City metropolitan area. The CVD risk factors analysed were BMI, blood pressure, plasma lipids levels, and fasting plasma glucose. Significantly higher levels of alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were observed in obese subjects, whereas significantly higher levels of DHA were observed in nonobese subjects. For CVD risk factors, ALA levels were positively correlated with plasma triglyceride concentrations and negatively associated with diastolic blood pressure. None of the CVD risk factors studied was linked to EPA levels. In addition, DPA was negatively related to high-density lipoprotein cholesterol (HDL-C) and positively correlated with the total cholesterol/HDL-C ratio. DHA levels were negatively correlated with BMI, waist circumference, and plasma triglyceride levels, whereas a positive association was observed with HDL-C levels. Total n-3 FA percentages were negatively correlated with BMI. In conclusion, higher DHA percentages in plasma PL are associated with a more favourable CVD risk profile, whereas higher DPA percentages in plasma PL are associated with a more deteriorated CVD risk profile.

Effects of age, sex, body mass index and APOE genotype on cardiovascular biomarker response to an n-3 polyunsaturated fatty acid supplementation.

OBJECTIVES: To test whether age, sex, body mass index (BMI), and the apolipoprotein E (APOE) genotype are associated with the metabolic response to an n-3 polyunsaturated fatty acid (PUFA) supplementation. METHODS: 210 subjects followed a 2-week run-in period based on Canada's Food Guide and underwent a 6-week 5 g/day fish oil supplementation (1.9 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Cardiovascular disease risk factors were measured. RESULTS: n-3 PUFA supplementation was associated with a decrease of plasma triglyceride levels (p = 0.0002) as well as with an increase of fasting glucose (FG) levels (p = 0.02). Age was associated with post-intervention plasma total cholesterol (p = 0.01), low-density lipoprotein cholesterol (p = 0.007), apolipoprotein B (p = 0.04), and insulin (p = 0.002) levels. Sex was associated with post-intervention plasma high-density lipoprotein cholesterol levels (p = 0.02). BMI was associated with plasma FG (p = 0.02) and insulin levels (p < 0.0001) after the supplementation. APOE genotype was associated with FG (p = 0.001) and C-reactive protein levels (p = 0.03) after the supplementation. CONCLUSION: Results suggest that age, sex, BMI, and the APOE genotype contribute to the inter-individual variability observed in the metabolic response to an n-3 PUFA supplementation.

Differences in metabolomic and transcriptomic profiles between responders and non-responders to an n-3 polyunsaturated fatty acids (PUFAs) supplementation.

Studies have demonstrated large within-population heterogeneity in plasma triacylglycerol (TG) response to n-3 PUFA supplementation. The objective of the study was to compare metabolomic and transcriptomic profiles of responders and non-responders of an n-3 PUFA supplementation. Thirty subjects completed a 2-week run-in period followed by a 6-week supplementation with n-3 PUFA (3 g/d). Six subjects did not lower their plasma TG (+9 %) levels (non-responders) and were matched to 6 subjects who lowered TG (-41 %) concentrations (responders) after the n-3 PUFA supplementation. Pre-n-3 PUFA supplementation characteristics did not differ between the non-responders and responders except for plasma glucose concentrations. In responders, changes were observed for plasma hexose concentrations, docosahexaenoic acid, stearoyl-CoA-desaturase-18 ratio, and the extent of saturation of glycerophosphatidylcholine after n-3 PUFA supplementation; however, no change in these parameters was observed in non-responders. Transcriptomic profiles after n-3 PUFA supplementation indicate changes in glycerophospholipid metabolism in both subgroups and sphingolipid metabolism in non-responders. Six key genes in lipid metabolism: fatty acid desaturase 2, phospholipase A2 group IVA, arachidonate 15-lipoxygenase, phosphatidylethanolamine N-methyltransferase, monoglyceride lipase, and glycerol-3-phosphate acyltransferase, were expressed in opposing direction between subgroups. In sum, results highlight key differences in lipid metabolism of non-responders compared to responders after an n-3 PUFA supplementation, which may explain the inter-individual variability in plasma TG response.

Relationship between the adoption of preventive practices and the metabolic profile of women with prior gestational diabetes mellitus.

Women with prior gestational diabetes mellitus (GDM) are encouraged to adopt healthy lifestyle behaviours to prevent or delay type 2 diabetes. The objective was to examine the association between the adoption of preventive practices and the metabolic profile of women with prior GDM. Analyses included 181 women who had GDM between 2003 and 2010. The preventive practices examined included (i) regular physical activity (≥150 min·week(-1)) assessed with the International Physical Activity Questionnaire; (ii) a healthy diet (score derived from the Alternate Healthy Eating Index and associated with a lower metabolic risk) evaluated from a food frequency questionnaire; and (iii) exclusive breastfeeding (≥6 months). Women were classified according to the number of preventive practices adopted. Waist circumference, weight, and height were measured and body mass index (BMI) was calculated. Fasting insulinemia and glycemia were obtained and Matsuda index for insulin sensitivity was calculated. Nearly one-third of women adopted none of the listed preventive practices. For each increase of 1 preventive practice adopted, women were 30% less likely to have a BMI ≥ 25 kg·m(-2) (odds ratio (OR): 0.70, 95% confidence interval (CI) (0.50-0.98)), they were 34% less likely to have a waist circumference ≥ 88 cm (OR: 0.66, 95%CI (0.47-0.92)) and they were 33% less likely to have a Matsuda index for insulin sensitivity < 9.69 (OR: 0.67, 95%CI (0.48-0.94)). These results suggest that women with prior GDM who adopt the recommended preventive practices in the years following delivery are less likely to have lower insulin sensitivity, less likely to be overweight-obese, and less likely to be characterized by abdominal obesity.

Associations between polymorphisms in genes involved in fatty acid metabolism and dietary fat intakes.

BACKGROUND: Obesity prevalence is growing in our population. Twin studies have estimated the heritability of dietary intakes to about 30%. The objective of this study was to verify whether polymorphisms in genes involved in fatty acid metabolism are associated with dietary fat intakes. METHODS: Seven hundred participants were recruited. A validated food frequency questionnaire was used to assess dietary intakes. PCR-RFLP and TAQMAN methodology were used to genotype PPARα Leu162Val, PPARγ Pro12Ala, PPARδ -87T>C, PPARGC1α Gly482Ser, FASN Val1483Ile and SREBF1 c.*619C>G. Statistical analyses were executed with SAS statistical package. RESULTS: Carriers of the Ala12 allele of PPARγ Pro12Ala polymorphism had higher intakes of total fat (p = 0.04). For FASN Val1483Ile polymorphism, significant gene-sex interaction effects were found for total fat and saturated fat intakes (p = 0.02 and p = 0.002, respectively). No significant difference in fat intakes was observed for PPARα Leu162Val, PPARδ -87T>C, PPARGC1α Gly482Ser and SREBF1 c.*619C>G polymorphisms. CONCLUSIONS: Polymorphisms in PPARγ and FASN seem to be associated with dietary fat intakes. Genetic variants are important to take into account when studying dietary intakes.

Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation.

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA.

Interaction between familial history of obesity and fat intakes on obesity phenotypes.

AIM: To evaluate whether familial history of obesity (FHO) interacts with dietary fat intake (DFI) on obesity-related phenotypes. METHODS: We recruited 664 participants aged between 18 and 55 years. A positive FHO (FHO+) was defined as having at least 1 obese first-degree relative and a negative FHO (FHO-) as no obese first-degree relative. Dietary intakes were collected from a food-frequency questionnaire. Body mass index, weight and waist girth were recorded using standard procedures. Fat mass and fat-free mass were assessed by electrical bioimpedance. RESULTS: Significant interaction effects (FHO x DFI) were observed for body mass index, weight, waist girth and fat mass (p interaction = 0.05, 0.04, 0.04, 0.02, respectively). Among FHO+ individuals, indices of obesity increased with an increasing amount of DFI, whereas these associations were not observed in FHO- individuals. We also found that FHO+ individuals consuming a high-fat diet were at higher risk of obesity than FHO- individuals consuming a low-fat diet (3.6, CI 2.1-6.2). CONCLUSION: These results suggest a stronger relationship between DFI and obesity-related phenotypes in individuals with FHO+.

Effect of the PPAR-Alpha L162V polymorphism on the cardiovascular disease risk factor in response to n-3 polyunsaturated fatty acids.

BACKGROUND: Dietary n-3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor-alpha (PPARalpha) can also modulate CVD risk factors. Since fatty acids, including n-3 PUFAs, are natural ligands of PPARalpha, a gene-diet interaction effect could be observed. AIMS: To examine whether n-3 PUFA- induced changes in CVD risk factors are influenced by the PPARalpha L162V polymorphism. METHODS: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. RESULTS: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p < 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). CONCLUSIONS: The PPARalpha L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n-3 PUFAs.

Impact of adiponectin gene polymorphisms on plasma lipoprotein and adiponectin concentrations of viscerally obese men.

The aim of this study was first to examine the relationships between adiponectin gene (Apm1) polymorphisms and anthropometric indices as well as plasma adiponectin and lipoprotein/lipid levels, and then to investigate whether the presence of visceral obesity or insulin resistance may modulate the impact of these polymorphisms on metabolic risk variables. Molecular screening of the Apm1 gene was achieved, and a sample of 270 unrelated men recruited from the greater Quebec City area and selected to cover a wide range of body fatness values was genotyped. Sequencing of the Apm1 gene revealed two previously reported polymorphisms (c.45T>G and c.276G>T) as well as two newly identified genetic variations (-13752delT and -13702G>C). Carriers of the c.276T allele had higher LDL-cholesterol and lower HDL-triglyceride concentrations than did 276G/G homozygotes (P=0.02 and P=0.01, respectively). Carriers of the c.45G allele exhibited higher plasma adiponectin concentrations than did 45T/T homozygotes (P=0.04). After dividing each genotype group into subgroups for visceral AT, homozygotes for the normal allele at position -13752delT, carriers of the c.45G allele, and carriers of the c.276T allele had similar total apolipoprotein B (apoB) concentrations, whether they were viscerally obese or not. These results suggest that some Apm1 gene polymorphisms influence plasma adiponectin concentrations and lipoprotein/lipid levels. In addition, the impact of these polymorphisms is modulated by the presence of visceral obesity.

Molecular screening of the microsomal triglyceride transfer protein: association between polymorphisms and both abdominal obesity and plasma apolipoprotein B concentration.

Microsomal triglyceride transfer protein (MTP) plays a critical role in the assembly of lipoproteins. The aim of this study was first to seek new MTP gene variants and then to verify whether MTP gene polymorphisms were associated with plasma lipoprotein/lipid levels in men with visceral obesity. Molecular screening of the MTP gene revealed 11 polymorphisms. The carriers of the c.933A allele and c.1151C allele or -400A/A homozygotes were characterized by increased levels of abdominal visceral adipose tissue (AT) measured by computed tomography (P=0.02, P=0.04, P=0.03, respectively). After dividing each genotype group into subgroups using 130 cm(2) as a cutoff point for visceral AT, significantly higher low-density lipoprotein (LDL)-apolipoprotein B (apoB) concentrations were found in obese men bearing the c.891G allele, the -400 T allele, as well as for 282G/G homozygotes, 933C/C homozygotes, and 1151A/A homozygotes when compared to their lean counterparts. Haplotypes were not associated with phenotypes under study. In conclusion, some MTP gene polymorphisms in the French Canadian population are associated with the amount of abdominal visceral AT and plasma LDL-apoB concentrations.