title: Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome.
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.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, B5 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kondo
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsukawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kumada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Morihiro
authors.initials: M
authors.lastname: Matsuda
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kihara
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Sumitsuji
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D052242:Adiponectin; D000368:Aged; D019943:Amino Acid Substitution; D001794:Blood Pressure; D015992:Body Mass Index; D003094:Collagen / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011506:Proteins / Q000235:genetics*; D012016:Reference Values
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D003094:Collagen