Open AccessIndependent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk
Author(s) -
Masayuki Sakiyama,
Hirotaka Matsuo,
Akira Akashi,
Seiko Shimizu,
Toshihide Higashino,
Makoto Kikuchi,
Akiyoshi Nakayama,
Mariko Naito,
Shinya Kawai,
Hiroshi Nakashima,
Yoshinori Sakurai,
Kimiyoshi Ichida,
Toru Shimizu,
Hiroshi Oda,
Nariyoshi Shinomiya
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-02528-z
Subject(s) - aldh2 , adh1b , gout , hyperuricemia , medicine , odds ratio , genome wide association study , alcohol dehydrogenase , genotyping , genetics , aldehyde dehydrogenase , uric acid , biology , single nucleotide polymorphism , genotype , alcohol , gene , enzyme , biochemistry , branched chain alpha keto acid dehydrogenase complex , dehydrogenase
Gout is caused by hyperuricemia, with alcohol consumption being an established risk factor. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are crucial enzymes for alcohol metabolism. We recently performed a genome-wide association study of gout and a subsequent fine-mapping study which identified rs671 of ALDH2 as a gout locus. However, the association between gout and common variants of ADH1B has hitherto remained unreported, prompting us to investigate the association between gout and common dysfunctional variants of ADH1B (rs1229984) and ALDH2 (rs671). We used 1,048 clinically defined gout cases and 1,334 controls of Japanese male. The “His carrier” (His/His or His/Arg) of rs1229984 (His48Arg) of ADH1B significantly increased gout risk ( P = 4.3 × 10 −4 , odds ratio = 1.76), as did the “non-Lys carrier (Glu/Glu)” of rs671 (Glu504Lys) of ALDH2 . Furthermore, common variants of ADH1B and ALDH2 are independently associated with gout. Our findings likewise suggest that genotyping these variants can be useful for the evaluation of gout risk.