Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence.
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.
Hinrichs
Anthony L
AL
Washington University School of Medicine, St. Louis, MO 63110, USA.
Wang
Jen C
JC
Bufe
Bernd
B
Kwon
Jennifer M
JM
Budde
John
J
Allen
Rebecca
R
Bertelsen
Sarah
S
Evans
Whitney
W
Dick
Danielle
D
Rice
John
J
Foroud
Tatiana
T
Nurnberger
John
J
Tischfield
Jay A
JA
Kuperman
Samuel
S
Crowe
Raymond
R
Hesselbrock
Victor
V
Schuckit
Marc
M
Almasy
Laura
L
Porjesz
Bernice
B
Edenberg
Howard J
HJ
Begleiter
Henri
H
Meyerhof
Wolfgang
W
Bierut
Laura J
LJ
Goate
Alison M
AM
D001741:Black or African American / Q000235:genetics; D000437:Alcoholism / Q000235:genetics*; D001483:Base Sequence; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000098706:Taste Receptors, Type 2
D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2