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

  • SAKIYAMA Masayuki
    Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College Department of Dermatology, 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
  • 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
  • SHIMIZU Toru
    Midorigaoka Hospital
  • SHINOMIYA Nariyoshi
    Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College

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

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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.<br>

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