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Diabetes 51:536-540, 2002
© 2002 by the American Diabetes Association, Inc.

Genetic Variation in the Gene Encoding Adiponectin Is Associated With an Increased Risk of Type 2 Diabetes in the Japanese Population

Kazuo Hara1,2,3, Philippe Boutin4, Yasumichi Mori1,4, Kazuyuki Tobe1,2, Christian Dina4, Kazuki Yasuda5, Toshimasa Yamauchi1,2, Shuichi Otabe6, Terumasa Okada1,5, Kazuhiro Eto1,2, Hiroko Kadowaki4, Ryoko Hagura4, Yasuo Akanuma2,4, Yoshio Yazaki5, Ryozo Nagai7, Matsuo Taniyama8, Koichi Matsubara9, Madoka Yoda10, Yasuko Nakano10, Satoshi Kimura1, Motowo Tomita10, Satoshi Kimura1, Chikako Ito11, Philippe Froguel4, and Takashi Kadowaki1,2

1 Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
2 CREST, Japan Science and Technology Corporation (JST), Tokyo, Japan
3 Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan
4 Institute of Biology-Centre National de la Recherche Scientifique (CNRS) 8090, Institute Pasteur de Lille, Lille, France
5 Department of Metabolic Disorder, Research Institute, International Medical Center of Japan, Tokyo, Japan
6 Department of Endocrinology and Metabolism, Kurume University School of Medicine, Kurume, Japan
7 Department of Cardiology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
8 3rd Department of Internal Medicine, Showa University, Tokyo, Japan
9 Chugai Diagnostics Science, Tokyo, Japan
10 Department of Physiological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan
11 Hiroshima Atomic Bomb Casualty Council Health Management Center, Hiroshima, Japan

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 µg/ml, G/T: 13.7 ± 0.87 µg/ml, T/T: 16.6 ± 2.24 µg/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.


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