Taste receptor polymorphisms in the Old Order Amish: Associations with obesity and related traits

Nutritional intake contributes to the development of human disease mainly by influencing the development of obesity-related conditions such as diabetes and cardiovascular disease. Orosensory variation strongly affects ingestive behavior and nutrient intake, while genetic variation in taste receptors (TRs) strongly affects taste sensitivity and food preference. Moreover, the expression of TRs in the gastrointestinal tract suggests that they may be involved in the nutrient-dependent regulation of metabolism. Therefore, we hypothesized that genetic variation in TRs may impact the development of obesity-related disease. To investigate these possibilities, we genotyped >60 haplotype-tagging single-nucleotide polymorphisms (SNPs) within 2 kB of all TAS1R and TAS2R genes in DNA samples from the Amish Family Diabetes Study. We identified candidate SNPs from the dbSNP and HapMap databases, and prioritized those with a minor allele frequency of ⩾0.2 in the CEU cohort (Utah residents with ancestry from northern and western Europe). We then evaluated the effects of genotype on 39 obesity-related traits (with adjustments for age, sex, and BMI). Several SNPs were significantly associated with obesity-related traits, including diabetes, glucose and insulin levels during oral glucose-tolerance tests, weight, and eating behaviors. We conclude that common variation in taste receptor genes may influence food preference, metabolism and/or risk factors associated with obesity. Support: NIDCD, NHLBI, NIDDK, UMSOM.