Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.
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.
Hara
Kazuo
K
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Boutin
Philippe
P
Mori
Yasumichi
Y
Tobe
Kazuyuki
K
Dina
Christian
C
Yasuda
Kazuki
K
Yamauchi
Toshimasa
T
Otabe
Shuichi
S
Okada
Terumasa
T
Eto
Kazuhiro
K
Kadowaki
Hiroko
H
Hagura
Ryoko
R
Akanuma
Yasuo
Y
Yazaki
Yoshio
Y
Nagai
Ryozo
R
Taniyama
Matsuo
M
Matsubara
Koichi
K
Yoda
Madoka
M
Nakano
Yasuko
Y
Tomita
Motowo
M
Kimura
Satoshi
S
Ito
Chikako
C
Froguel
Philippe
P
Kadowaki
Takashi
T
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
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins