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

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Author(s)

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

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 (<i>OAT4/SLC22A11</i>) is expressed in the kidney and mediates urate transport, we investigated the effects of a common variant of <i>OAT4/SLC22A11</i> 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 <i>OAT4/SLC22A11</i> 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 <i>OAT4/SLC22A11</i> is associated with RUE type gout, a major gout subtype.<br>

Journal

  • Drug Metabolism and Pharmacokinetics

    Drug Metabolism and Pharmacokinetics 29(2), 208-210, 2014

    The Japanese Society for the Study of Xenobiotics

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