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. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | 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 |
Volume | 61 |
Issue | 7 |
Pagination | 1888-94 |
Date Published | 2012 Jul |
ISSN | 1939-327X |
Keywords | Adult, Aged, Blood Glucose, Diabetes Mellitus, Type 2, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Humans, Indians, North American, Insulin, Insulin Resistance, Male, Middle Aged, Pedigree, Polymorphism, Single Nucleotide, Receptors, Nicotinic, Smoking, Young Adult |
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. |
DOI | 10.2337/db11-1393 |
Alternate Journal | Diabetes |
PubMed ID | 22586585 |
Grant List | R21-HL-092363 / HL / NHLBI NIH HHS / United States U01-HL-65520 / HL / NHLBI NIH HHS / United States U01-HL-41642 / HL / NHLBI NIH HHS / United States U01-HL-41654 / HL / NHLBI NIH HHS / United States K01-AG-034259 / AG / NIA NIH HHS / United States U01-HL-65521 / HL / NHLBI NIH HHS / United States U01-HL-41652 / HL / NHLBI NIH HHS / United States |
Related Faculty:
Ying Zhang, M.D., Ph.D.