Elsevier

Appetite

Volume 54, Issue 1, February 2010, Pages 93-99
Appetite

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

https://doi.org/10.1016/j.appet.2009.09.011Get rights and content

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.

Introduction

Taste strongly affects ingestive behavior and nutrient intake. An individual's sensitivity to the tastes evoked by certain compounds in foods (i.e., sweet, salty, sour, bitter) is strongly affected by genetic variation (Bachmanov and Beauchamp, 2007, Bufe et al., 2005, Fushan et al., 2009, Kim et al., 2003, Kim et al., 2006, Pronin et al., 2007). The best studied human taste phenotype is the relative sensitivity of individuals to the bitter taste evoked by any variety of compounds that containing a Nsingle bondCdouble bondS (thiourea) moiety, such as phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) (see Wooding, 2006, for a review). A moderate perception of bitterness can be appealing and expected in a variety of foods (e.g., alcohol and cheeses). However, compounds perceived as intensely bitter are usually rejected by humans and other mammals, likely because bitter taste is closely associated with the presence of toxins (e.g., Ames et al., 1990, Bravo, 1998, Fenwick et al., 1983, Tepper, 2008). For example, a large body of research indicates that adults who possess an enhanced perception of PROP avoid certain bitter-tasting foods, including specific fruits and vegetables (Dinehart et al., 2006, Drewnowski et al., 2000, Drewnowski et al., 1999, Drewnowski et al., 1997, Drewnowski et al., 1998, Fischer et al., 1961, Glanville and Kaplan, 1965, Jerzsa-Latta et al., 1990, Tepper et al., 2008b) (although see Drewnowski et al., 2007, Mattes and Labov, 1989). Thus, taste sensitivity to PROP is often used as a marker for individual differences in taste perception that influences food preferences and intake (e.g., Dinehart et al., 2006, Duffy and Bartoshuk, 2000, Tepper, 2008).

The principal genetic determinants of phenotypic variation in PROP/PTC taste sensitivity are alleles of the gene TAS2R38 (Bufe et al., 2005, Kim et al., 2003). This gene, which contains a single coding exon approximately 1 kb in size, encodes a chemosensory receptor sensitive to PROP, PTC, and many other thiourea-containing compounds (Bufe et al., 2005, Kim et al., 2003, Prodi et al., 2004). Three nonsynonymous coding SNPs within TAS2R38 (rs713598 – G145C, Ala49Pro; rs1726866 – T785C, Val262Ala; rs10246939 – A886G, Ile296Val) give rise to several haplotypes, only two of which (Pro-Ala-Val (PAV) and Ala-Val-Ile (AVI)) are commonly found in human populations (Kim et al., 2005, Wooding et al., 2004). Individuals who possess at least one copy of the PAV allele are significantly more sensitive to PROP (Bufe et al., 2005) or PTC (Kim et al., 2003) than are those who are homozygous for the AVI allele. These haplotypes are also correlated with bitterness perception of plants, (e.g., turnips, broccoli, watercress) that synthesize glucosinolates, a class of compounds that also contain the thiourea moiety (Sandell & Breslin, 2006). These associations suggest that variation within TAS2R38 may also influence the ingestion of certain foods. Indeed, individuals who posses at least one copy of the PROP sensitive allele of TAS2R38 eat fewer cruciferous vegetables than do adults who are homozygous for the PROP insensitive allele (Sacerdote et al., 2007).

Members of the TAS2R family are expressed in the gustatory system, where they function as bitter taste receptors. However, it is now clear that TAS2Rs and other chemosensory receptors are also expressed in cells of the gastrointestinal (GI) tract and associated organs, suggesting that they may be involved in the nutrient-dependent regulation of metabolism. Components of the taste transduction cascade, including TAS2Rs, are expressed in the cells of the stomach and small intestine (e.g., Bezencon et al., 2007, Rozengurt and Sternini, 2007, Rozengurt et al., 2006, Wu et al., 2002), where they can mediate insulin release from the pancreas (Nakagawa et al., 2009), the incretin response to sweet- and bitter-tasting compounds (Dotson et al., 2008, Jang et al., 2007, Jeon et al., 2008), glucose assimilation (Mace et al., 2007, Mace et al., 2009, Margolskee et al., 2007) and the secretion of cholecystokinin (CCK) from enteroendocrine cells (Jeon et al., 2008). Thus, because both the gustatory and digestive systems use TAS2Rs to detect substances present in food, polymorphisms in these receptors could impact ingestive behaviors either by affecting taste sensitivity or by influencing the postprandial response to nutrients.

When attempting to maintain a healthy lifestyle, an individual's eating patterns are as important as what they eat (e.g., Greenwood and Stanford, 2008, Haines and Neumark-Sztainer, 2006). These patterns are known to be heritable (de Krom et al., 2009, Steinle et al., 2002, Tholin et al., 2005) and related to weight gain and BMI (Bryant et al., 2008, Hays and Roberts, 2008, Keskitalo et al., 2008). The Three-Factor Eating Questionnaire assesses three behavioral traits related to the control of food intake: restraint, disinhibition, and hunger (Stunkard and Messick, 1985, Stunkard and Wadden, 1990). Restraint is an avoidance of eating to control body weight. Disinhibition is loss of restraint that results in overeating. Hunger measures the perceived need for food. It has been suggested that variation in taste function could influence eating behaviors (de Krom et al., 2009, Murphy and Kemmotsu, 2009). Interestingly, the behavioral trait restraint mitigates the relationship between PROP taster status and adiposity in women (Tepper et al., 2008a). However, it remains unclear whether a direct relationship exists between eating behaviors and TAS2R38 genotype. To investigate this issue, we examined whether differences in restraint, disinhibition and hunger are associated with TAS2R38 variants in an Old Order Amish population.

Section snippets

Subjects

The University of Maryland School of Medicine's Institutional Review Board approved all studies. The Amish Family Diabetes Study (AFDS) is an ongoing effort to identify genetic contributors to obesity, diabetes, cardiovascular disease and related disorders (Damcott et al., 2006, Hsueh et al., 2000, Steinle et al., 2002). Detailed descriptions of the population (the Old Order Amish of Lancaster County, Pennsylvania, USA), study design, recruitment methods, phenotypic characterization, clinical

Results

We first asked whether a variant in the taste receptor gene TAS2R38 was associated with eating behaviors as assessed by the Three-Factor Eating Questionnaire (Stunkard and Messick, 1985, Stunkard and Wadden, 1990). We performed association analysis of the SNP rs1726866, a nonsynonymous coding SNP within TAS2R38 (T785C; Val262Ala), and the eating behaviors hunger, restraint and disinhibition. The “C” allele of rs1726866, the minor allele in the AFDS, is strongly associated with increased taste

Discussion

TAS2R38 genotype may influence the types of food an individual prefers or consumes (Sacerdote et al., 2007, Sandell and Breslin, 2006), or possibly an individual's postprandial response to ingested nutrients (Chen, Wu, Reeve, & Rozengurt, 2006). However, it was not known whether TAS2R38 genotype influences how one eats. Here we have identified an important link between chemosensory receptor gene variation and the control of eating. Our study indicates an association between the major allele

Acknowledgements

We thank the Munger lab for helpful discussions, X. Shi, L. Reinhart for technical assistance, and the AFDS participants. This work was supported by grants from the NIDCD (DC005786, DC010110 to S.D.M.), NHLBI (HL076768 to N.I.S.), the University of Maryland School of Medicine, and the Clinical Nutrition Research Unit of Maryland (DK072488). C.D.D. was supported by NIDCD and NIDCR training grants.

References (81)

  • V.B. Duffy et al.

    Food acceptance and genetic variation in taste

    Journal of the American Dietetic Association

    (2000)
  • A.A. Fushan et al.

    Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose

    Current Biology

    (2009)
  • N.P. Hays et al.

    Eating behavior correlates of adult weight gain and obesity in healthy women aged 55–65 years

    American Journal of Clinical Nutrition

    (2002)
  • M. Jerzsa-Latta et al.

    Use and perceived attributes of cruciferous vegetables in terms of genetically mediated taste sensitivity

    Appetite

    (1990)
  • K. Keskitalo et al.

    The Three-Factor Eating Questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations

    American Journal of Clinical Nutrition

    (2008)
  • R. Mattes et al.

    Bitter taste responses to phenylthiocarbamide are not related to dietary goitrogen intake in human beings

    Journal of the American Dietetic Association

    (1989)
  • A.N. Pronin et al.

    Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin

    Current Biology

    (2007)
  • E. Rozengurt et al.

    Taste receptor signaling in the mammalian gut

    Current Opinion in Pharmacology

    (2007)
  • M.A. Sandell et al.

    Variability in a taste-receptor gene determines whether we taste toxins in food

    Current Biology

    (2006)
  • J.S. Savage et al.

    Dieting, restraint, and disinhibition predict women's weight change over 6 years

    American Journal of Clinical Nutrition

    (2009)
  • N. Soranzo et al.

    Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16

    Current Biology

    (2005)
  • N.I. Steinle et al.

    Eating behavior in the Old Order Amish: heritability analysis and a genome-wide linkage analysis

    American Journal of Clinical Nutrition

    (2002)
  • A.J. Stunkard et al.

    The Three-Factor Eating Questionnaire to measure dietary restraint, disinhibition and hunger

    Journal of Psychosomatic Research

    (1985)
  • B.J. Tepper et al.

    Influence of genetic taste sensitivity to 6-n-propylthiouracil (PROP), dietary restraint and disinhibition on body mass index in middle-aged women

    Physiology and Behaviour

    (2002)
  • S. Tholin et al.

    Genetic and environmental influences on eating behavior: the Swedish Young Male Twins Study

    American Journal of Clinical Nutrition

    (2005)
  • N.J. Timpson et al.

    TAS2R38 (phenylthiocarbamide) haplotypes, coronary heart disease traits, and eating behavior in the British Women's Heart and Health Study

    American Journal of Clinical Nutrition

    (2005)
  • N.V. Ullrich et al.

    PROP taster status and self-perceived food adventurousness influence food preferences

    Journal of the American Dietetic Association

    (2004)
  • D.A. Williamson et al.

    Association of body mass with dietary restraint and disinhibition

    Appetite

    (1995)
  • S. Wooding et al.

    Natural selection and molecular evolution in PTC, a bitter-taste receptor gene

    American Journal of Human Genetics

    (2004)
  • B.N. Ames et al.

    Dietary pesticides (99.99% all natural)

    Proceedings of the National Academy of Sciences of the United States of America

    (1990)
  • A.A. Bachmanov et al.

    Taste receptor genes

    Annual Review of Nutrition

    (2007)
  • R.M. Baron et al.

    The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations

    Journal of Personality and Social Psychology

    (1986)
  • J.C. Barrett et al.

    Haploview: analysis and visualization of LD and haplotype maps

    Bioinformatics

    (2005)
  • C. Bezencon et al.

    Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells

    Chemical Senses

    (2007)
  • L. Bravo

    Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance

    Nutrition Reviews

    (1998)
  • E.J. Bryant et al.

    Disinhibition: its effects on appetite and weight regulation

    Obesity Reviews

    (2008)
  • M.C. Chen et al.

    Bitter stimuli induce Ca2+ signaling and CCK release in enteroendocrine STC-1 cells: role of L-type voltage-sensitive Ca2+ channels

    American Journal of Physiology-Cell Physiology

    (2006)
  • C.M. Damcott et al.

    Polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are associated with type 2 diabetes in the Amish: replication and evidence for a role in both insulin secretion and insulin resistance

    Diabetes

    (2006)
  • M. de Krom et al.

    Genetic variation and effects on human eating behavior

    Annual Review of Nutrition

    (2009)
  • M. de Krom et al.

    Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns

    Diabetes

    (2007)
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