title: Common missense variant of monocarboxylate transporter 9 (MCT9/SLC16A9) gene is associated with renal overload gout, but not with all gout susceptibility.
abstract: Gout is a common disease caused by hyperuricemia, which shows elevated serum uric acid (SUA) levels. From a viewpoint of urate handling in humans, gout patients can be divided into those with renal overload (ROL) gout with intestinal urate underexcretion, and those with renal underexcretion (RUE) gout. Recent genome-wide association studies (GWAS) revealed an association between SUA and a variant in human monocarboxylate transporter 9 (MCT9/SLC16A9) gene. Although the function of MCT9 remains unclear, urate is mostly excreted via intestine and kidney where MCT9 expression is observed. In this study, we investigated the relationship between a variant of MCT9 and gout in 545 patients and 1,115 healthy volunteers. A missense variant of MCT9 (K258T), rs2242206, significantly increased the risk of ROL gout (p = 0.012), with odds ratio (OR) of 1.28, although it revealed no significant association with all gout cases (p = 0.10), non-ROL gout cases (p = 0.83), and RUE gout cases (p = 0.34). In any case groups and the control group, minor allele frequencies of rs2242206 were >0.40. Therefore, rs2242206 is a common missense variant and is revealed to have an association with ROL gout, indicating that rs2242206 relates to decreased intestinal urate excretion rather than decreased renal urate excretion. Our study provides clues to better understand the pathophysiology of gout as well as the physiological roles of MCT9.
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.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Takuya
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiraku
authors.initials: H
authors.lastname: Ogata
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Takada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Chisaki
authors.initials: C
authors.lastname: Ushiyama
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Inoue
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D000368:Aged; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006073:Gout / Q000235:genetics*; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000502:physiology*; D020125:Mutation, Missense; D012306:Risk; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
chemical_list: D027501:Monocarboxylic Acid Transporters; C549233:SLC16A9 protein, human; D014527:Uric Acid