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  • Title: A gene-family analysis of 61 genetic variants in the nicotinic acetylcholine receptor genes for insulin resistance and type 2 diabetes in American Indians.
    Author: Yang J, Zhu Y, Cole SA, Haack K, Zhang Y, Beebe LA, Howard BV, Best LG, Devereux RB, Henderson JA, Henderson P, Lee ET, Zhao J.
    Journal: Diabetes; 2012 Jul; 61(7):1888-94. PubMed ID: 22586585.
    Abstract:
    Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the nicotinic acetylcholine receptor (nAChR) genes have been associated with smoking phenotypes and are likely to influence diabetes. Although each single variant may have only a minor effect, the joint contribution of multiple single nucleotide polymorphisms (SNPs) to the occurrence of disease may be larger. In this study, we conducted a gene-family analysis to investigate the joint impact of 61 tag SNPs in 7 nAChRs genes on insulin resistance and type 2 diabetes in 3,665 American Indians recruited by the Strong Heart Family Study. Results show that although multiple SNPs showed marginal individual association with insulin resistance and type 2 diabetes, only a few can pass adjustment for multiple testing. However, a gene-family analysis considering the joint impact of all 61 SNPs reveals significant association of the nAChR gene family with both insulin resistance and type 2 diabetes (both P < 0.0001), suggesting that genetic variants in the nAChR genes jointly contribute to insulin resistance and type 2 diabetes among American Indians. The effects of these genetic variants on insulin resistance and diabetes are independent of cigarette smoking per se.
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