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

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.