RT Journal Article SR Electronic T1 Association of Adiponectin Mutation With Type 2 Diabetes JF Diabetes JO Diabetes FD American Diabetes Association SP 2325 OP 2328 DO 10.2337/diabetes.51.7.2325 VO 51 IS 7 A1 Kondo, Hidehiko A1 Shimomura, Iichiro A1 Matsukawa, Yuko A1 Kumada, Masahiro A1 Takahashi, Masahiko A1 Matsuda, Morihiro A1 Ouchi, Noriyuki A1 Kihara, Shinji A1 Kawamoto, Toshiharu A1 Sumitsuji, Satoru A1 Funahashi, Tohru A1 Matsuzawa, Yuji YR 2002 UL http://diabetes.diabetesjournals.org/content/51/7/2325.abstract AB 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.