The haplotypes of the IRS-2 gene affect insulin sensitivity in Japanese patients with type 2 diabetes
The haplotypes of the IRS-2 gene affect insulin sensitivity in Japanese patients with type 2 diabetes
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DOI：
10.1016/j.diabres.2004.08.009
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发表时间：
2005-04-01
影响因子：
5.1
通讯作者：
Nakao, K
中科院分区：
文献类型：
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作者：
Okazawa, K;Yoshimasa, Y;Nakao, K
胰岛素受体底物2（IRS-2）基因第1057位氨基酸从甘氨酸到天冬酰胺酸（G1057 D）的常见核苷酸多态性最近被证明是葡萄糖耐受个体和2型糖尿病患者胰岛素敏感性的决定因素。关于后者，IRS-2 D1057等位基因增加肥胖个体中胰岛素抵抗的风险。在我们从G1057 D变异体和新发现的-769C/T替换重建单倍型后，我们研究了IRS-2基因影响日本葡萄糖耐受受试者（n = 260）和2型糖尿病患者（n = 123）胰岛素敏感性的可能性。我们没有发现D1057等位基因和单倍型对与糖尿病风险相关。然而，2型糖尿病患者，特别是肥胖患者，携带D1057等位基因和CA单倍型与胰岛素抵抗有关。此外，我们认为TG和CG单倍型可能对胰岛素抵抗具有保护作用。这一观察结果提出了IRS-2 D1057等位基因和CA单倍型都是用于识别特别易受胰岛素抵抗影响的肥胖个体的有用遗传标记的可能性。(c)2004爱思唯尔爱尔兰有限公司保留所有权利。
A commonly occurring nucleotide polymorphism of the insulin-receptor substrate 2 (IRS-2) gene at amino acid 1057 from Glycine to Asparaginic acid (G1057D) was recently shown to be a determinant of insulin sensitivity in both glucose-tolerant individuals and those with type 2 diabetes. With respect to the latter, the IRS-2 D1057 allele increase the risk of insulin resistance among obese individuals. After we reconstructed haplotypes from the G1057D variant and the -769C/T replacement that was newly identified, we investigated the possibility that the IRS-2 gene affects insulin sensitivity in Japanese glucose-tolerant subjects (n = 260) and type 2 diabetic patients (n = 123). We did not find that the D1057 allele and haplotype pairs were associated with the risk of diabetes. However, type 2 diabetic patients, particularly obese patients, carrying the D 1057 allele and the CA haplotype were associated with insulin resistance. Furthermore, we suggested that the TG and CG haplotypes might have a protective role against insulin resistance. This observation raises the possibility that both the IRS-2 D1057 allele and the CA haplotype are useful genetic markers for identifying obese individuals who are particularly susceptible to insulin resistance. (c) 2004 Elsevier Ireland Ltd. All rights reserved.