Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population
Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population
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DOI：
10.2337/diabetes.51.2.536
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发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Kadowaki, T
中科院分区：
文献类型：
--
作者：
Hara, K;Boutin, P;Kadowaki, T
脂肪细胞衍生的肽脂联素（也称为 GBP28）在 2 型糖尿病患者中减少。最近的全基因组扫描将糖尿病易感基因座定位到染色体 3q27，即脂联素基因 (APM1) 所在的位置。在此，我们提出了脂联素基因第 45 位和第 276 位的频繁单核苷酸多态性与 2 型糖尿病之间存在关联的证据（分别为 P = 0.003 和 P = 0.002）。与在位置 45 和位置 276 具有 T/T 基因型的受试者相比，在位置 45 具有 G/G 基因型或在位置 276 具有 GIG 基因型的受试者患 2 型糖尿病的风险显着增加（比值比分别为 1.70 [95% CI 1.09-2.65] 和 2.16 [1.22-3.95]）。此外，276位G/G基因型受试者的胰岛素抵抗指数高于TIT基因型受试者（1.61+/-0.05 vs.1.19+/-0.12，P=0.001）。 BMI 较高的受试者中，第 276 位的 G 等位基因与较低的血浆脂联素水平呈线性相关（G/G：10.4 +/- 0.85 mug/ml，G/T：13.7 +/- 0.87 mug/ml，T/T：16.6 +/- 2.24 mug/ml，P = 0.01）。基于这些发现以及脂联素改善动物模型胰岛素敏感性的观察，我们得出结论，脂联素基因可能是2型糖尿病的易感基因。
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 GIG 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 TIT 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 mug/ml, G/T: 13.7 +/- 0.87 mug/ml, T/T: 16.6 +/- 2.24 mug/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.