TY  - JOUR
PY  - 2011//
TI  - Confirmation of ALDH2 as a Major Locus of Drinking Behavior and of Its Variants Regulating Multiple Metabolic Phenotypes in a Japanese Population
JO  - Circulation journal
A1  - Takeuchi, Fumihiko
A1  - Isono, Masato
A1  - Nabika, Toru
A1  - Katsuya, Tomohiro
A1  - Sugiyama, Takao
A1  - Yamaguchi, Shuhei
A1  - Kobayashi, Shotai
A1  - Ogihara, Toshio
A1  - Yamori, Yukio
A1  - Fujioka, Akihiro
A1  - Kato, Norihiro
SP  - 911
EP  - 918
VL  - 75
IS  - 4
N2  - Background: Normative alcohol use (or drinking behavior) influences the risk of cardiovascular disease in a multi-faceted manner. To identify susceptibility gene variants for drinking behavior, a 2-staged genome-wide association study was performed in a Japanese population. Methods and Results: In the stage-1 scan, 733 cases and 729 controls were genotyped with 456,827 SNP markers. The associated loci without redundancy of linkage disequilibrium were further examined in the stage-2 general population panel comprising 2,794 drinkers (≥once per week), 1,521 chance drinkers (<once per week), and 1,351 non-drinkers. Along with genome-wide exploration, we aimed to replicate the trait association of a candidate gene SNP previously reported (rs1229984 in ADH1B). A cluster of 12 SNPs on 12q24 were found to significantly (P<5×10(-8)) associate with drinking behavior in stage 1, among which rs671 (a Glu-to-Lys substitution at position 504) in the ALDH2 gene showed the strongest association (odds ratio (OR)=0.16, P=3.6×10(-211) in the joint analysis). The association was also replicated for rs1229984 (OR=1.20, P<3.6×10(-4)). Furthermore, ALDH2 504Lys was associated with several metabolic traits, eg, lower levels of high-density lipoprotein cholesterol and liver enzymes-AST, ALT, and γGTP-by interacting with alcohol intake. Conclusions: Our results confirm ALDH2 as a major locus regulating drinking behavior in the Japanese, indicating that the ALDH2 504Lys variant exerts pleiotropic effects on risk factors of cardiovascular disease among drinkers.<p />  <p>Language: en</p>
LA  - en
SN  - 1346-9843
UR  - http://dx.doi.org/
ID  - ref1
ER  -