title: Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.
abstract: An adipocyte-derived peptide, adiponectin (also known as GBP28), is decreased in subjects with type 2 diabetes. Recent genome-wide scans have mapped a diabetes susceptibility locus to chromosome 3q27, where the adiponectin gene (APM1) is located. Herein, we present evidence of an association between frequent single nucleotide polymorphisms at positions 45 and 276 in the adiponectin gene and type 2 diabetes (P = 0.003 and P = 0.002, respectively). Subjects with the G/G genotype at position 45 or the G/G genotype at position 276 had a significantly increased risk of type 2 diabetes (odds ratio 1.70 [95% CI 1.09-2.65] and 2.16 [1.22-3.95], respectively) compared with those having the T/T genotype at positions 45 and 276, respectively. In addition, the subjects with the G/G genotype at position 276 had a higher insulin resistance index than those with the T/T genotype (1.61 +/- 0.05 vs. 1.19 +/- 0.12, P = 0.001). The G allele at position 276 was linearly associated with lower plasma adiponectin levels (G/G: 10.4 +/- 0.85 microg/ml, G/T: 13.7 +/- 0.87 microg/ml, T/T: 16.6 +/- 2.24 microg/ml, P = 0.01) in subjects with higher BMIs. Based on these findings together with the observation that adiponectin improves insulin sensitivity in animal models, we conclude that the adiponectin gene may be a susceptibility gene for type 2 diabetes.
authors.affiliation: Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Philippe
authors.initials: P
authors.lastname: Boutin
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Mori
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Christian
authors.initials: C
authors.lastname: Dina
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yasuda
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Otabe
authors.forename: Terumasa
authors.initials: T
authors.lastname: Okada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Eto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kadowaki
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hagura
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Akanuma
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yazaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Matsuo
authors.initials: M
authors.lastname: Taniyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Madoka
authors.initials: M
authors.lastname: Yoda
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Motowo
authors.initials: M
authors.lastname: Tomita
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kimura
authors.forename: Chikako
authors.initials: C
authors.lastname: Ito
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
mesh_terms: D052242:Adiponectin; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D012306:Risk
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins