Insulin receptor substrate 1 (IRS1) Variants Confer Risk of Diabetes in the Boston Puerto Rican Health Study

胰岛素受体底物1（IRS1）多态性与糖尿病危险因素有关（波士顿波多黎各人群健康研究）

Xiang Feng ； Katherine L Tucker ； Laurence D Parnell ； Jian Shen ； Yu-Chi Lee ； José M Ordovás ； Wen-Hua Ling ； Chao-Qiang Lai

《Asia Pacific Journal of Clinical Nutrition》 22卷1期 (2013/03) Pp. 150-159

https://doi.org/10.6133/apjcn.2013.22.1.09

摘要

目的：目前关于IRS1多态性与2型糖尿病及危险因素的关联研究结果并不一致。在波士顿波多黎各人群健康研究的对象中研究IRS1基因多态性与2型糖尿病及危险因素，包括胰岛素抵抗、高血糖血症和DNA损伤等的关联作用。对象与方法：测定1132例波多黎各成人中IRS1基因6个SNP並分析其与2型糖尿病及危险因素之间的关联。结果：SNP rs934167和rs1801123与空腹血糖含量有显著性关联（p=0.005 和p=0.016），rs934167与血浆胰岛素水平也呈显著性关联（p=0.005）。rs934167小等位基因携带者的HOMA-IR指数显著较高，而QUICKI指数显著较低（p=0.001和p=0.001）；他们发生高血糖血症和高胰岛素血症的危险性分别增加了40%和58%（OR=1.40和1.58，p=0.005和p=0.016）。然而，他们罹患2型糖尿病的危险性只是轻度增高（OR=1.27，p=0.077）。进一步发现，rs934167和rs1801123小等位基因单倍型C-T携带者显示了类似的关联（经过多重检验校正后）。此外，G972R（rs1801278）小等位基因与较高的DNA损伤水平-尿8-OHdG（p=0.020）和血浆CRP水平（p=0.035）有显著性关联。结论：在成年波多黎各人中，IRS1基因多态性与2型糖尿病危险因素有关。同时有新的发现，即IRS1多态性位点G972R（rs1801278）可能与DNA氧化损伤和炎症有关。

關鍵字

基因多态性 ； IRS1 ； 2型糖尿病 ； 胰岛素抵抗 ； DNA损伤

並列摘要

Objective: Published data concerning associations between IRS1 variants and type 2 diabetes and related traits have been inconsistent. We examined the relationship between common variants in IRS1, type 2 diabetes, and related traits including insulin resistance, hyperglycemia and DNA damage in the Boston Puerto Rican Health Study. Methods: We genotyped six common IRS1 variants in an adult Puerto Rican population (n=1132) and tested for association with risk of type 2 diabetes and related traits. Results: SNPs rs934167 and rs1801123 showed significant association with fasting glucose concentrations (p=0.005 and p=0.016, respectively) and rs934167 showed significant association with plasma insulin levels (p=0.005). Carriers of the rs934167 minor allele had significantly higher HOMA-IR and lower QUICKI (p=0.001 and p=0.001, respectively), and a 40% and 58% greater likelihood of being hyperglycaemic or hyperinsulinemic (OR=1.40 and 1.58; p=0.013 and 0.002, respectively). However, they exhibited only a marginally significant trend towards having type 2 diabetes (OR=1.27, p =0.077). Furthermore, carriers of the haplotype C-T of the rs934167 and rs1801123 minor alleles showed consistent patterns of associations after correction for multiple testing. In addition, the G972R (rs1801278) minor allele was significantly associated with higher urinary 8-OHdG concentrations (p=0.020) and plasma CRP levels (p=0.035). Conclusions: Our results support IRS1 variants associated with type 2 diabetes risk in adult Puerto Ricans. Moreover, we report the novel finding that IRS1 variant G972R (rs1801278) may contribute to oxidative DNA damage and inflammation.

並列關鍵字

genetic association ； IRS1 ； type 2 diabetes ； insulin resistance ； DNA damage

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