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 transmittance of taste perception have previously demonstrated a correlation between genetic variation in TAS2R38 and sensitivity to bitter-taste compounds such as phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP). Haplotypes resulting from 3 common nonsynonymous coding single-nucleotide polymorphisms in the TAS2R38 gene have been shown to alter receptor functions and taste sensitivity to PTC and PROP. The perceived bitterness of PROP has also been associated with oral sensation and drinking behaviors.


METHODS
We used family-based association methods to test for association between TAS2R38 haplotypes and alcohol dependence as well as a measure of alcohol consumption (Maxdrinks) and age of onset of drinking behaviors in a sample of families densely affected with alcoholism. We have also extended our analysis of TAS2R16 to include the Maxdrinks phenotype.


RESULTS
A positive correlation was observed between TAS2R38 haplotypes and Maxdrinks in Collaborative Study on the Genetics of Alcoholism (COGA) high-risk women of African-American origin. The common taster haplotype is significantly associated with a lower mean Maxdrinks compared with the other haplotypes. Similarly, the allele of TAS2R16 that is associated with a lower risk for alcohol dependence is also associated with lower mean Maxdrinks scores in African-American families. In contrast to the previously reported significant association between TAS2R16 and alcohol dependence, we found no evidence that TAS2R38 haplotypes influence alcohol dependence in the COGA dataset.


CONCLUSIONS
Functional variants in both TAS2R16 and TAS2R38 correlate with alcohol consumption in African-American families.
Wang
Jen C
JC
Washington University in St. Louis, MO 63110, USA.
Hinrichs
Anthony L
AL
Bertelsen
Sarah
S
Stock
Heather
H
Budde
John P
JP
Dick
Danielle M
DM
Bucholz
Kathleen K
KK
Rice
John
J
Saccone
Nancy
N
Edenberg
Howard J
HJ
Hesselbrock
Victor
V
Kuperman
Samuel
S
Schuckit
Marc A
MA
Bierut
Laura J
LJ
Goate
Alison M
AM
D001741:Black or African American / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics* / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D010670:Phenylthiourea / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D013649:Taste / Q000235:genetics / Q000502:physiology; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism; D000098706:Taste Receptors, Type 2
D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; C056698:6-n-propyluracil; D014498:Uracil; D010670:Phenylthiourea