Association of Adiponectin Mutation With Type 2 Diabetes

A Candidate Gene for the Insulin Resistance Syndrome

  1. Hidehiko Kondo1,
  2. Iichiro Shimomura1,
  3. Yuko Matsukawa1,
  4. Masahiro Kumada1,
  5. Masahiko Takahashi1,
  6. Morihiro Matsuda1,
  7. Noriyuki Ouchi1,
  8. Shinji Kihara1,
  9. Toshiharu Kawamoto2,
  10. Satoru Sumitsuji3,
  11. Tohru Funahashi1 and
  12. Yuji Matsuzawa1
  1. 1Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan
  2. 2National Hospital Kure Medical Center, Hiroshima, Japan
  3. 3Izumisano City Hospital, Osaka, Japan

    Abstract

    Adiponectin, also referred to as AdipoQ or ACRP30, is a plasma protein produced and secreted exclusively from adipose tissue. The protein contains a collagen-like domain and a C1q-like globular domain. A protease-generated globular segment enhances fatty acid oxidation in muscles, thereby modulating lipid and glucose metabolism. Plasma adiponectin levels are inversely correlated with the severity of insulin resistance. A recent genome-wide scan study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. Here, we screened Japanese patients with type 2 diabetes and age- and BMI-matched nondiabetic control subjects for mutations in adiponectin gene. We identified four missense mutations (R112C, I164T, R221S, and H241P) in the globular domain. Among these mutations, the frequency of I164T mutation was significantly higher in type 2 diabetic patients than in age- and BMI- matched control subjects (P < 0.01). Furthermore, plasma adiponectin concentrations of subjects carrying I164T mutation were lower than those of subjects without the mutation. All the subjects carrying I164T mutation showed some feature of metabolic syndrome, including hypertension, hyperlipidemia, diabetes, and atherosclerosis. Our findings suggest that I164T mutation is associated with low plasma adiponectin concentration and type 2 diabetes.

    Footnotes

    • Address correspondence and reprint requests to Tohru Funahashi, Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine, B5 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan. E-mail: tohru{at}imed2.med.osaka-u.ac.jp.

      Received for publication 25 January 2002 and accepted in revised form 10 April 2002.

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