Bénédicte Fontaine-Bisson

Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations

Glucose sensing in the brain has been proposed to be involved in regulating food intake, but the mechanism is not known. Glucose transporter type 2 (GLUT2)-null mice fail to control their food intake in response to glucose, suggesting a potential role for this transporter as a glucose sensor in the brain. Here we show that individuals with a genetic variation in GLUT2 (Thr110Ile) have a higher daily intake of sugars in two distinct populations. In the first population, compared with individuals with the Thr/Thr genotype, carriers of the Ile allele had a significantly higher intake of sugars as assessed from 3-day food records administered on two separate visits (visit 1: 112 +/- 9 vs. 86 +/- 4 g/day, P = 0.01; visit 2: 111 +/- 8 vs. 82 +/- 4 g/day, P = 0.003), demonstrating within-population reproducibility. In a second population, carriers of the Ile allele also reported consuming a significantly greater intake of sugars (131 +/- 5 vs. 115 +/- 3 g/day, P = 0.007) over a 1-mo period as measured from a food frequency questionnaire. GLUT2 genotypes were not associated with fat, protein, or alcohol intake in either population. These observations were consistent across older and younger adults as well as among subjects with early Type 2 diabetes and healthy individuals. Taken together, our findings show that a genetic variation in GLUT2 is associated with habitual consumption of sugars, suggesting an underlying glucose-sensing mechanism that regulates food intake.

Functional genetic variants of glutathione S-transferase protect against serum ascorbic acid deficiency

BACKGROUND Glutathione S-transferases (GSTs) are detoxifying enzymes that contribute to the glutathione-ascorbic acid (vitamin C) antioxidant cycle. OBJECTIVE The objective was to determine whether GST genotypes modify the association between dietary vitamin C and serum ascorbic acid. DESIGN Nonsmoking men and women (n = 905) between 20 and 29 y of age were participants in the Toronto Nutrigenomics and Health Study. Overnight fasting blood samples were collected to determine serum ascorbic acid concentrations by HPLC and to genotype for deletion polymorphisms in GSTM1 and GSTT1 and an Ile105Val substitution in GSTP1. A 196-item food-frequency questionnaire was used to estimate vitamin C intake. RESULTS A gene-diet interaction on serum ascorbic acid was observed for GSTM1 (P = 0.04) and GSTT1 (P = 0.01) but not for GSTP1 (P = 0.83). The odds ratio (95% CI) for serum ascorbic acid deficiency (<11 micromol/L) was 3.20 (1.88, 5.44) for subjects who did not meet the Recommended Dietary Allowance of vitamin C compared with those who did. The corresponding odds ratios (95% CIs) were 2.17 (1.10, 4.28) and 12.28 (4.26, 33.42), respectively, for individuals with the GSTT1*1/*1 +*1/*0 (functional) and GSTT1*0/*0 (null) genotypes and 2.29 (0.96, 5.45) and 4.03 (2.01, 8.09), respectively, for the GSTM1*1/*1+GSTM1*1/*0 and GSTM1*0/*0 genotypes. CONCLUSIONS The recommended intake of vitamin C protects against serum ascorbic acid deficiency, regardless of genotype. Individuals with GST null genotypes had an increased risk of deficiency if they did not meet the Recommended Dietary Allowance for vitamin C, which suggests that the GST enzymes protect against serum ascorbic acid deficiency when dietary vitamin C is insufficient.

Nutrigenomics of Taste – Impact on Food Preferences and Food Production

Food preferences are influenced by a number of factors such as personal experiences, cultural adaptations and perceived health benefits. Taste, however, is the most important determinant of how much a food is liked or disliked. Based on the response to bitter-tasting compounds such as phenylthiocarbamide (PTC) or 6-n-propylthiouracil (PROP), individuals can be classified as supertasters, tasters or nontasters. Sensitivity to bitter-tasting compounds is a genetic trait that has been recognized for more than 70 years. Genetic differences in bitter taste perception may account for individual differences in food preferences. Other factors such as age, sex and ethnicity may also modify the response to bitter-tasting compounds. There are several members of the TAS2R receptor gene family that encode taste receptors on the tongue, and genetic polymorphisms of TAS2R38 have been associated with marked differences in the perception of PTC and PROP. However, the association between TAS2R38 genotypes and aversion to bitter-tasting foods is not clear. Single nucleotide polymorphisms in other taste receptor genes have recently been identified, but their role in bitter taste perception is not known. Establishing a genetic basis for food likes/dislikes may explain, in part, some of the inconsistencies among epidemiologic studies relating diet to risk of chronic diseases. Identifying populations with preferences for particular flavors or foods may lead to the development of novel food products targeted to specific genotypes or ethnic populations.

Evaluating the discriminative power of multi-trait genetic risk scores for type 2 diabetes in a northern Swedish population

Aims/hypothesisWe determined whether single nucleotide polymorphisms (SNPs) previously associated with diabetogenic traits improve the discriminative power of a type 2 diabetes genetic risk score.MethodsParticipants (n = 2,751) were genotyped for 73 SNPs previously associated with type 2 diabetes, fasting glucose/insulin concentrations, obesity or lipid levels, from which five genetic risk scores (one for each of the four traits and one combining all SNPs) were computed. Type 2 diabetes patients and non-diabetic controls (n = 1,327/1,424) were identified using medical records in addition to an independent oral glucose tolerance test.ResultsModel 1, including only SNPs associated with type 2 diabetes, had a discriminative power of 0.591 (p < 1.00 × 10−20 vs null model) as estimated by the area under the receiver operator characteristic curve (ROC AUC). Model 2, including only fasting glucose/insulin SNPs, had a significantly higher discriminative power than the null model (ROC AUC 0.543; p = 9.38 × 10−6 vs null model), but lower discriminative power than model 1 (p = 5.92 × 10−5). Model 3, with only lipid-associated SNPs, had significantly higher discriminative power than the null model (ROC AUC 0.565; p = 1.44 × 10−9) and was not statistically different from model 1 (p = 0.083). The ROC AUC of model 4, which included only obesity SNPs, was 0.557 (p = 2.30 × 10−7 vs null model) and smaller than model 1 (p = 0.025). Finally, the model including all SNPs yielded a significant improvement in discriminative power compared with the null model (p < 1.0 × 10−20) and model 1 (p = 1.32 × 10−5); its ROC AUC was 0.626.Conclusions/interpretationAdding SNPs previously associated with fasting glucose, insulin, lipids or obesity to a genetic risk score for type 2 diabetes significantly increases the power to discriminate between people with and without clinically manifest type 2 diabetes compared with a model including only conventional type 2 diabetes loci.

Obesity and type 2 diabetes in Northern Canada's remote First Nations communities: the dietary dilemma.

First Nations populations in Northwestern Ontario have undergone profound dietary and lifestyle transformations in less than 50 years, which have contributed to the alarming rise in obesity and obesity-related diseases, in particular type 2 diabetes mellitus. Even though the genetic background of First Nations peoples differs from that of the Caucasians, genetics alone cannot explain such a high prevalence in obesity and type 2 diabetes. Modifications in lifestyle and diet are major contributors for the high prevalence of chronic diseases. What remains constant in the literature is the persistent view that locally harvested and prepared foods are of tremendous value to First Nations peoples providing important health and cultural benefits that are increasingly being undermined by western-based food habits. However, the complexities of maintaining a traditional diet require a multifaceted approach, which acknowledges the relationship between benefits, risks and viability that cannot be achieved using purely conventional medical and biological approaches. This brief review explores the biological predispositions and potential environmental factors that contribute to the development of the high incidence of obesity and obesity-related diseases in First Nations communities in Northern Canada. It also highlights some of the complexities of establishing exact physiological causes and providing effective solutions.

NF-κB -94Ins/Del ATTG polymorphism modifies the association between dietary polyunsaturated fatty acids and HDL-cholesterol in two distinct populations.

We previously showed that polymorphisms in the tumor necrosis factor (TNF)-alpha gene, which is regulated by nuclear factor kappa B (NF-kappaB), modify the association between dietary polyunsaturated fatty acid (PUFA) intake and circulating HDL-cholesterol. Our objective was to determine whether a common polymorphism in the NFKB1 gene (-94Ins/Del ATTG) interacts with PUFA intake to affect HDL-cholesterol in two distinct populations. Participants were diabetes-free young adults (n=593) and older individuals with diet-treated type 2 diabetes (n=103). The NF-kappaB polymorphism modified the association between dietary PUFA intake and HDL-cholesterol in both populations (p=0.02 and 0.005 for interaction). Among individuals with the Ins/Ins genotype, each 1% increase in energy from PUFA was associated with a 0.03+/-0.01 mmol/L (p for slope=0.009) and 0.06+/-0.02 mmol/L (p=0.02) increase in HDL-cholesterol among participants from the diabetes-free and diabetic populations. An inverse relationship was observed among those with the Del/Del genotype, which was significantly different from that of the Ins/Ins groups in both populations (p=0.02 and 0.006). No effects were observed for the Ins/Del genotype in either population (p>0.05). These findings show that this functional polymorphism in the NF-kB gene modifies the association between PUFA intake and plasma HDL-cholesterol in two distinct populations.

Effect of an Oat Bran-Rich Supplement on the Metabolic Profile of Overweight Premenopausal Women

Background/Aims: A healthy diet is a key factor in the prevention of cardiovascular disease, the leading cause of death for women in industrialized countries. In this regard, soluble fibers may have beneficial effects on the plasma lipoprotein/lipid profile. The objective of the present study was to investigate the plasma lipoprotein/lipid response to dietary fibers in overweight premenopausal women within a randomized controlled trial. Methods: Following a 2-week run-in phase, 34 premenopausal women (age: 22–53 years) were randomly assigned either to the control group (no supplement) or to the treatment group, which received 2 oat bran-enriched muffins per day (28 g/day of oat bran) during 4 weeks. Results: Supplementation with oat bran had a beneficial effect on plasma HDL-C levels. Indeed, compared to the control group (n = 16), a mean increase in plasma HDL-C levels of 11.2% was observed in women eating the oat bran supplement (n = 18) (p = 0.01), whereas the total cholesterol/HDL-C ratio decreased by 7.0% (p = 0.002). Results were similar after adjustment for age, apo E genotype and weight change. Conclusion: These results suggest that oat bran-rich foods have beneficial effect on the metabolic profile of overweight women. Integration of these foods as part of a healthy diet may, therefore, improve the cardiovascular risk profile of women.

Genetic Polymorphisms of Tumor Necrosis Factor-Alpha Modify the Association between Dietary Polyunsaturated Fatty Acids and Plasma High-Density Lipoprotein-Cholesterol Concentrations in a Population of Young Adults

Background/Aims: Genetic polymorphisms in tumor necrosis factor-α (TNF-α) modify the association between polyunsaturated fatty acids (PUFA) and plasma high-density lipoprotein (HDL) cholesterol in a population with type 2 diabetes. The objective of this study was to determine whether this gene × diet interaction is observed in a diabetes-free population and whether it is due to n–3 or n–6 PUFA. Methods: Subjects (n = 595) were aged 20–29 years and genotyped for the TNF-α –238G>A and TNF-α –308G>A polymorphisms. Diet was assessed using a food frequency questionnaire. Subjects were grouped as having no minor A allele at both the –238 and –308 positions (0/0), or one minor A allele at either the –238 (1/0) or the –308 (0/1) position. Results: TNF-α genotypes modified the association between dietary PUFA and HDL-cholesterol concentrations (p = 0.04 for interaction). Among individuals with the 0/0 genotype, total PUFA was positively associated with HDL-cholesterol in both men (p = 0.008) and women (p = 0.03), and for both n–6 (p = 0.004) and n–3 (p = 0.04) PUFA. However, an inverse relationship was observed among men carrying the 1/0 genotype (p = 0.005). Conclusion: These findings demonstrate that TNF-α genotypes modify the association between dietary PUFA and HDL-cholesterol and provide further evidence that inflammation is involved in the reverse cholesterol transport.

Melanin-concentrating hormone receptor 1 polymorphisms are associated with components of energy balance in the Complex Diseases in the Newfoundland Population: Environment and Genetics (CODING) study

BACKGROUND The melanin-concentrating hormone receptor 1 (MCHR1) is a G protein-coupled receptor that regulates energy balance and body composition in animal models. Inconsistent effects of MCHR1 polymorphisms on energy homeostasis in humans may partly be attributable to environmental factors. OBJECTIVES We examined the effect of 4 single nucleotide polymorphisms (rs133073, rs133074, rs9611386, and rs882111) in the MCHR1 gene on body composition as well as energy-related lifestyle factors (diet and physical activity). We also examined the effect of gene-lifestyle interactions on body composition. DESIGN A total of 1153 participants (248 men and 905 women) from the cross-sectional Complex Diseases in the Newfoundland Population: Environment and Genetics (CODING) study were genotyped by using probe-based chemistry validated assays. Diet and physical activity were estimated by using validated frequency questionnaires, and body composition was assessed by using dual-energy X-ray absorptiometry. RESULTS Three polymorphisms (rs9611386, rs882111, and rs133073) were associated with differences in body-composition measurements (all P < 0.05). There was an interaction between rs9611386 and carbohydrate intake on total mass and waist circumference (both P ≤ 0.01). There was also an interaction between rs9611386 and body mass index categories (normal weight, overweight, and obese) on energy intakes (P = 0.02). A similar interaction was shown with rs882111 (P = 0.02). Interactions were also observed between each of these polymorphisms (rs9611386, rs882111, and rs133073) and physical activity score on body-composition measurements (all P < 0.05). CONCLUSION These findings suggest that polymorphisms in the MCHR1 gene are associated with differences in body composition and interact with physiologic and energy-related lifestyle factors.

Association of vitronectin and plasminogen activator inhibitor-1 levels with the risk of metabolic syndrome and type 2 diabetes mellitus. Results from the D.E.S.I.R. prospective cohort.

It was the objective of this study to investigate the relation between vitronectin and plasminogen activator inhibitor (PAI)-1 plasma levels with nine-year incidences of the metabolic syndrome (MetS) and of type 2 diabetes mellitus (T2DM). Baseline plasma concentrations of vitronectin and PAI-1 were measured in 627 healthy participants from the prospective D.E.S.I.R. cohort who subsequently developed MetS (n = 487) and T2DM (n = 182) over a nine-year follow-up (42 presented both) and who were matched with two healthy control subjects each by use of a nested case-control design. Parameters composing the MetS explained about 20% of plasma vitronectin levels. An increase of one standard deviation of vitronectin was associated with increased risks of both the MetS (odds ratio [OR] = 1.21 [1.07 - 1.37], p = 0.003) and T2DM (OR = 1.24 [1.01 - 1.53], p = 0.045). Corresponding ORs for PAI-1 levels were 1.46 [1.27 - 1.68] (p<10(-4)) and 1.40 [1.14 - 1.72] (p = 0.0012). However, the effects of vitronectin and PAI-1 levels on outcomes were not independent. The vitronectin-MetS association was restricted to individuals with low to modest PAI-1 levels (OR = 1.33 [1.14 - 1.54], p = 0.0003) while no association was observed in individuals with high PAI-1 levels (OR = 0.87 [0.68 - 1.10], p = 0.24), the test for interaction being highly significant (p = 0.0009). In conclusion, baseline plasma vitronectin is a marker of incident MetS at nine years. Its predictive ability for MetS and T2DM should not be assessed independently of PAI-1 levels.