title: Identification of rs671, a common variant of ALDH2, as a gout susceptibility locus.
abstract: Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10(-18), odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that "A" allele (Lys) of rs671 plays a protective role in the development of gout.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.|Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-0801, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Department of Medical Chemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.affiliation: Laboratory for Mathematics, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.affiliation: Ryougoku East Gate Clinic, 3-21-1 Ryougoku, Sumida-ku, Tokyo 130-0026, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ooyama
authors.affiliation: Kyoto Industrial Health Association, 67 Kitatsuboi-cho, Nishinokyo, Nakagyo-ku, Kyoto 604-8472, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D002874:Chromosome Mapping; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006073:Gout / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D020641:Polymorphism, Single Nucleotide
chemical_list: C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial