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.