A Common Variant of Organic Anion Transporter 4 (OAT4/SLC22A11) Gene Is Associated with Renal Underexcretion Type Gout

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

doi:10.2133/dmpk.DMPK-13-NT-070

Notes

A Common Variant of Organic Anion Transporter 4 (OAT4/SLC22A11) Gene Is Associated with Renal Underexcretion Type Gout

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

Author information

Masayuki SAKIYAMA
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
Department of Dermatology, National Defense Medical College
Hirotaka MATSUO
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
Seiko SHIMIZU
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
Hiroshi NAKASHIMA
Department of Preventive Medicine and Public Health, National Defense Medical College
Akiyoshi NAKAYAMA
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
Toshinori CHIBA
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College
Mariko NAITO
Department of Preventive Medicine, Nagoya University Graduate School of Medicine
Tappei TAKADA
Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo
Hiroshi SUZUKI
Department of Pharmacy, the University of Tokyo Hospital, Faculty of Medicine, the University of Tokyo
Nobuyuki HAMAJIMA
Department of Healthcare Administration, Nagoya University Graduate School of Medicine
Kimiyoshi ICHIDA
Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences
Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine
Toru SHIMIZU
Midorigaoka Hospital
Nariyoshi SHINOMIYA
Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College

Keywords: SLC transporter, urate transporter, gouty arthritis, subtype analysis, clinical classification

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Supplementary material

2014 Volume 29 Issue 2 Pages 208-210

DOI https://doi.org/10.2133/dmpk.DMPK-13-NT-070

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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.

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