Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence.

نویسندگان

  • Anthony L Hinrichs
  • Jen C Wang
  • Bernd Bufe
  • Jennifer M Kwon
  • John Budde
  • Rebecca Allen
  • Sarah Bertelsen
  • Whitney Evans
  • Danielle Dick
  • John Rice
  • Tatiana Foroud
  • John Nurnberger
  • Jay A Tischfield
  • Samuel Kuperman
  • Raymond Crowe
  • Victor Hesselbrock
  • Marc Schuckit
  • Laura Almasy
  • Bernice Porjesz
  • Howard J Edenberg
  • Henri Begleiter
  • Wolfgang Meyerhof
  • Laura J Bierut
  • Alison M Goate
چکیده

A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta -glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta -glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans (minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Characterization of the β-d-Glucopyranoside Binding Site of the Human Bitter Taste Receptor hTAS2R16*

G-protein-coupled receptors mediate the senses of taste, smell, and vision in mammals. Humans recognize thousands of compounds as bitter, and this response is mediated by the hTAS2R family, which is one of the G-protein-coupled receptors composed of only 25 receptors. However, structural information on these receptors is limited. To address the molecular basis of bitter tastant discrimination b...

متن کامل

Probenecid Inhibits the Human Bitter Taste Receptor TAS2R16 and Suppresses Bitter Perception of Salicin

Bitter taste stimuli are detected by a diverse family of G protein-coupled receptors (GPCRs) expressed in gustatory cells. Each bitter taste receptor (TAS2R) responds to an array of compounds, many of which are toxic and can be found in nature. For example, human TAS2R16 (hTAS2R16) responds to β-glucosides such as salicin, and hTAS2R38 responds to thiourea-containing molecules such as glucosino...

متن کامل

Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin.

BACKGROUND A novel family of G protein-coupled receptors, TAS2Rs, has recently been characterized and linked to sensitivity to bitter taste compounds. We have previously reported that a missense mutation in the TAS2R16 gene reduces the sensitivity of the receptor to bitter-taste stimuli and that it is associated with risk for alcohol dependence. Other family-based studies on the genetic transmi...

متن کامل

Ric-8A, a Gα Protein Guanine Nucleotide Exchange Factor Potentiates Taste Receptor Signaling

Taste receptors for sweet, bitter and umami tastants are G-protein-coupled receptors (GPCRs). While much effort has been devoted to understanding G-protein-receptor interactions and identifying the components of the signalling cascade downstream of these receptors, at the level of the G-protein the modulation of receptor signal transduction remains relatively unexplored. In this regard a taste-...

متن کامل

Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception

The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • American journal of human genetics

دوره 78 1  شماره 

صفحات  -

تاریخ انتشار 2006