A common variant of organic anion transporter 4 (OAT4/SLC22A11) gene is associated with renal underexcretion type gout.

Drug metabolism and pharmacokinetics 2014

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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.

Citation

Masayuki Sakiyama, Hirotaka Matsuo, Seiko Shimizu, Hiroshi Nakashima, Akiyoshi Nakayama, Toshinori Chiba, Mariko Naito, Tappei Takada, Hiroshi Suzuki, Nobuyuki Hamajima, Kimiyoshi Ichida, Toru Shimizu, Nariyoshi Shinomiya. A common variant of organic anion transporter 4 (OAT4/SLC22A11) gene is associated with renal underexcretion type gout. Drug metabolism and pharmacokinetics. 2014;29(2):208-10