Karen M. Eny

Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations

BACKGROUND Taste is an important determinant of food consumption, and genetic variations in the sweet taste receptor subunit TAS1R2 may contribute to interindividual variations in sugar consumption. OBJECTIVE We determined whether Ser9Cys and Ile191Val variations in TAS1R2 were associated with differences in the consumption of sugars in 2 populations. DESIGN Population 1 included 1037 diabetes-free young adults in whom we assessed dietary intake by using a 1-mo, 196-item food-frequency questionnaire. Population 2 consisted of 100 individuals with type 2 diabetes with dietary intakes assessed by using 2 sets of 3-d food records administered 2 wk apart. Dietary counseling was provided between food records 1 and 2. Dietary intakes between genotypes were compared by using analysis of covariance adjusted for potential confounders. RESULTS In population 1, a significant Ile191Val × body mass index (BMI; in kg/m²) interaction was detected for the consumption of sugars, and the effect of genotype was significant only in individuals with a BMI ≥ 25 (n = 205). In comparison with individuals homozygous for the Ile allele, Val carriers consumed fewer sugars (122 ± 6 compared with 103 ± 6 g sugar/d, respectively; P = 0.01). Regression estimates that associated BMI with total sugar consumption by Ile/Ile and Val-carrier genotype intersected at a BMI of 23.5. In population 2, Val carriers also consumed less sugar than did individuals with the Ile/Ile genotype (99 ± 6 compared with 83 ± 6 g sugar/d, respectively; P = 0.04) on food record 2, and sugar was the only macronutrient that decreased significantly (-9 ± 4 g sugar/d, P = 0.02) in Val carriers who received dietary counseling. CONCLUSION Our findings show that a genetic variation in TAS1R2 affects habitual consumption of sugars and may contribute to interindividual differences in changing behaviors in response to dietary counseling.

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.

Comparison of body mass index and waist circumference as predictors of cardiometabolic health in a population of young Canadian adults

BackgroundThis study aimed to investigate whether waist circumference (WC) or body mass index (BMI) is a better predictor of blood lipid concentrations among young men and women from different ethnocultural groups.MethodsParticipants were 1181 healthy men (n = 358) and women (n = 823) aged 20-29 years taken from the cross-sectional Toronto Nutrigenomics and Health Study. Analyses were conducted separately for men and women, and for Caucasian and East Asian ethnocultural groups. Serum triglycerides (TG) and total to HDL cholesterol ratio (TC:HDL cholesterol) were used as outcomes. Associations between the adiposity and blood lipid measures were examined using partial correlations and odds ratios derived from logistic regression models.ResultsWC had a stronger association with serum lipid concentrations than BMI. WC was significantly related to TG and TC:HDL cholesterol after adjusting for BMI and covariates among men and women (P ≤ 0.01). However, after adjusting for WC and covariates, BMI was not significantly associated with the two serum lipid measures. WC was a better predictor of TG and TC:HDL among all sex and ethnocultural subgroups except among East Asian women where little difference between the two measures was observed.ConclusionsWC is a stronger predictor of cardiometabolic health when compared with BMI among young adults, especially among men.

Dopamine D2 Receptor Genotype (C957T) and Habitual Consumption of Sugars in a Free-Living Population of Men and Women

Background/Aims: The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. Methods: Caucasian men (n = 96) and women (n = 217) 20–29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. Results: Among men, consumption of sucrose was 60 ± 6, 48 ± 4, and 39 ± 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 ± 4, 53 ± 2, and 44 ± 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. Conclusions: These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption.

Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars

Background/Aims: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. Methods: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796). Sucrose taste thresholds were determined by staircase procedure (solutions: 9 × 10-6 to 0.5 mol/l). Suprathreshold sensitivity to 0.01-1.0 mol/l sucrose solutions was assessed using general Labeled Magnitude Scales. Results: A significant genotype-BMI interaction was observed for rs12033832 (G>A) for suprathreshold sensitivity (p = 0.01) and sugar intake (p = 0.003). Among participants with a BMI ≥25, G allele carriers had lower sensitivity ratings (mean incremental area under the taste sensitivity curve ± SE; GG/GA 54.4 ± 4.1 vs. AA 178.5 ± 66.6; p = 0.006), higher thresholds (GG/GA 9.3 ± 1.1 vs. AA 4.4 ± 4.3 mmol/l; p = 0.004) and consumed more sugars (GG/GA 130 ± 4 vs. AA 94 ± 13 g/day; p = 0.009). G allele carriers with a BMI <25 had lower thresholds (GG/GA 8.6 ± 0.5 vs. AA 16.7 ± 5.7 mmol/l; p = 0.02) and consumed less sugars (GG/GA 122 ± 2 vs. AA 145 ± 8 g/day; p = 0.004). Conclusion: The rs12033832 single nucleotide polymorphism in TAS1R2 is associated with sucrose taste and sugar intake, but the effect differs depending on BMI.

Genetic Variants Associated with Circulating Parathyroid Hormone

Parathyroid hormone (PTH) is a primary calcium regulatory hormone. Elevated serum PTH concentrations in primary and secondary hyperparathyroidism have been associated with bone disease, hypertension, and in some studies, cardiovascular mortality. Genetic causes of variation in circulating PTH concentrations are incompletely understood. We performed a genome-wide association study of serum PTH concentrations among 29,155 participants of European ancestry from 13 cohort studies (n=22,653 and n=6502 in discovery and replication analyses, respectively). We evaluated the association of single nucleotide polymorphisms (SNPs) with natural log-transformed PTH concentration adjusted for age, sex, season, study site, and principal components of ancestry. We discovered associations of SNPs from five independent regions with serum PTH concentration, including the strongest association with rs6127099 upstream of CYP24A1 (P=4.2 × 10-53), a gene that encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-dihydroxyvitamin D. Each additional copy of the minor allele at this SNP associated with 7% higher serum PTH concentration. The other SNPs associated with serum PTH concentration included rs4074995 within RGS14 (P=6.6 × 10-17), rs219779 adjacent to CLDN14 (P=3.5 × 10-16), rs4443100 near RTDR1 (P=8.7 × 10-9), and rs73186030 near CASR (P=4.8 × 10-8). Of these five SNPs, rs6127099, rs4074995, and rs219779 replicated. Thus, common genetic variants located near genes involved in vitamin D metabolism and calcium and renal phosphate transport associated with differences in circulating PTH concentrations. Future studies could identify the causal variants at these loci, and the clinical and functional relevance of these variants should be pursued.

ISNN Society News

Michel de Lorgeril La Tronche (Grenoble) Serge Ferrari Geneva Steve Humphries London Jing X. Kang Charlestown, Mass. Ronald Krauss Oakland, Calif. Sergio Muntoni Cagliari Gérard Siest Nancy Marjanne Senekal Cape Town Lisa A. Spence Rosemont, Ill. Antonio Velazquez Mexico City Nikos Yiannakouris Athens Aims and Scope The purpose of the society is to increase understanding through research and education of professionals and the general public of the role of genetic variation and dietary response and the role of nutrients in gene expression.

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