Independent effects of ADH1B and ALDH2 common dysfunctional variants on gout risk

• Published in: Scientific reports Vol. 7; no. 1; pp. 2500 - 6
• Main Authors: Sakiyama, Masayuki, Matsuo, Hirotaka, Akashi, Airi, Shimizu, Seiko, Higashino, Toshihide, Kawaguchi, Makoto, Nakayama, Akiyoshi, Naito, Mariko, Kawai, Sayo, Nakashima, Hiroshi, Sakurai, Yutaka, Ichida, Kimiyoshi, Shimizu, Toru, Ooyama, Hiroshi, Shinomiya, Nariyoshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31.05.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 45; 631/208/205; 692/699/2743; Adult; Alcohol; Alcohol dehydrogenase; Alcohol Dehydrogenase - genetics; Alcohol Drinking; Aldehyde dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial - genetics; Aldehydes; Dehydrogenase; Dehydrogenases; Gene mapping; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genotype; Genotyping; Gout; Gout - genetics; Gout - pathology; Humanities and Social Sciences; Humans; Hyperuricemia; Male; Middle Aged; multidisciplinary; Polymorphism, Single Nucleotide; Risk Factors; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-02528-z

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.