Variation in the gene TAS2R38 is associated with the eating behavior disinhibition in Old Order Amish women

Abstract

Insensitivity to the bitter-tasting compound 6-n-propylthiouracil (PROP) has been proposed as a marker for individual differences in taste perception that influence food preference and intake. The principal genetic determinants of phenotypic variation in PROP taste sensitivity are alleles of the TAS2R38 gene, which encodes a chemosensory receptor sensitive to thiourea compounds including PROP and phenylthiocarbamide. Members of the TAS2R family are expressed in the gustatory system, where they function as bitter taste receptors, and throughout the gut, where their physiological roles in prandial, gut-derived hormone release are beginning to be elucidated. To better understand the relationship between TAS2R function and ingestive behaviors, we asked if TAS2R38 variants are associated with one or more of three eating behaviors: restraint, disinhibition, and hunger. We genotyped a single nucleotide polymorphism (SNP) located within the TAS2R38 gene, rs1726866 (T785C, Val262Ala) in 729 nondiabetic individuals (381 females, 348 males) within the Amish Family Diabetes Study. Eating behaviors were assessed using the Three-Factor Eating Questionnaire. An association analysis between rs1726866 and these three traits revealed a significant association of the PROP-insensitive “T” allele with increased disinhibition (p = 0.03). Because eating behaviors differ substantially between males and females, we subsequently performed sex-stratified analyses, which revealed a strong association in females (p = 0.0002) but not in males. Analyses with other SNPs in close proximity to rs1726866 suggest that this locus is principally responsible for the association. Therefore, our results indicate that a polymorphism in TAS2R38 is associated with differences in ingestive behavior.

Taste buds: cells, signals and synapses

“…An evolutionary note in this context is that orthologous receptors in mice and humans often are responsive to very different bitter tastants 54 , which suggests that receptors have been reassigned to ecologically relevant compounds and that the gene family has been subjected to selective pressures 55 . Many T2Rs exhibit functional polymorphisms that result in varying abilities to taste particular compounds 56 , and these polymorphisms may underlie differences in food preference 57 (BOX 3). …”

Genetics of eating behavior: established and emerging concepts

“…Heritability and linkage analysis of eating behavior measured by the TFQ provides evidence that these behavior traits are heritable 15,16 . Although much remains to be understood about the genes regulating these behaviors, genetic influence of disinhibition has been linked to neuromedin , a factor mediating satiety , in a French Canadian cohort and to TAS2R38 , a bitter taste receptor, in a cohort of Amish women 16,17 . GAD (glutamic acid decarboxylase) has also been linked to eating behavior.…”

Taste perception, associated hormonal modulation, and nutrient intake

“…Amish women with the T allele (T785C) reported higher disinhibition when eating behavior was assessed using the three-factor eating questionnaire. 114 TAS1R2 and TAS1R3 are genes that encode the heterodimer of G protein-coupled receptors that are responsible for detection of natural and artificial sweeteners. The five receptor sites within the heterodimer may exist for various structural classes of sweeteners.…”