Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.

Kazuo Hara , Philippe Boutin (1) , Yasumichi Mori , Kazuyuki Tobe , Christian Dina (1) , Kazuki Yasuda , Toshimasa Yamauchi , Shuichi Otabe , Terumasa Okada (2) , Kazuhiro Eto , Hiroko Kadowaki , Ryoko Hagura , Yasuo Akanuma , Yoshio Yazaki , Ryozo Nagai , Matsuo Taniyama , Koichi Matsubara , Madoka Yoda , Yasuko Nakano , Motowo Tomita , Satoshi Kimura , Chikako Ito , Philippe Froguel (1, 3, 4) , Takashi Kadowaki

1 GMM - Génétique des maladies multifactorielles
2 Itoh laboratory, Division of Materials Physics
3 Section of Genomic Medicine
4 Genome Centre

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.

Domaines: Génétique humaine

Kazuo Hara, Philippe Boutin, Yasumichi Mori, Kazuyuki Tobe, Christian Dina, et al.. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.. Diabetes, 2002, 51 (2), pp.536-40. ⟨hal-00174757⟩