title: A common variant of organic anion transporter 4 (OAT4/SLC22A11) gene is associated with renal underexcretion type gout.
abstract: Gout, a common disease, is a consequence of hyperuricemia, and increases the risks of hypertension, cardiovascular diseases, cerebrovascular diseases and renal failure. Gout can be classified into 3 types: the renal underexcretion (RUE) type, renal overload type and combined type. RUE type is a major type of gout; however, its genetic causes are still unclear. Since human organic anion transporter 4 (OAT4/SLC22A11) is expressed in the kidney and mediates urate transport, we investigated the effects of a common variant of OAT4/SLC22A11 on the susceptibility to gout. Five hundred and forty-five Japanese male gout cases and 1,115 male individuals as a control group were genotyped with rs17300741, a single nucleotide polymorphism in the OAT4/SLC22A11 gene. The association analysis of rs17300741 showed no significant association for all gout cases; however, there was a slight but significant association for RUE type gout cases (p = 0.049). These results also suggest that OAT4 contributes to urate transport at the apical membrane of renal proximal tubule cells in humans. Our findings make it clear for the first time that a common variant of OAT4/SLC22A11 is associated with RUE type gout, a major gout subtype.
authors.affiliation: Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sakiyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsuo
authors.forename: Seiko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nakayama
authors.forename: Toshinori
authors.initials: T
authors.lastname: Chiba
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Ichida
authors.forename: Toru
authors.initials: T
authors.lastname: Shimizu
authors.forename: Nariyoshi
authors.initials: N
authors.lastname: Shinomiya
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006073:Gout / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007564:Japan; D007668:Kidney / Q000378:metabolism*; D008297:Male; D016017:Odds Ratio; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics* / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065667:Renal Elimination / Q000235:genetics*; D012307:Risk Factors; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D029362:Organic Anion Transporters, Sodium-Independent; C427207:SLC22A11 protein, human; D014527:Uric Acid