A Gene-Family Analysis of 61 Genetic Variants in the Nicotinic Acetylcholine Receptor Genes for Insulin Resistance and Type 2 Diabetes in American Indians
- Jingyun Yang1,
- Yun Zhu1,
- Shelley A. Cole2,
- Karin Haack2,
- Ying Zhang3,
- Laura A. Beebe1,
- Barbara V. Howard4,
- Lyle G. Best5,
- Richard B. Devereux6,
- Jeffrey A. Henderson7,
- Patricia Henderson7,
- Elisa T. Lee1,3 and
- Jinying Zhao1⇓
- 1University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- 2Texas Biomedical Research Institute, San Antonio, Texas
- 3Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
- 4MedStar Health Research Institute, Hyattsville, Maryland; the Georgetown-Howard Universities Center for Clinical and Translational Sciences, Washington, District of Columbia
- 5Missouri Breaks Industries Research Inc, Timber Lake, South Dakota
- 6New York Hospital-Cornell Medical Center, New York, New York
- 7Black Hills Center for American Indian Health, Rapid City, South Dakota
- Corresponding author: Jinying Zhao, .
Cigarette smoking is a risk factor for type 2 diabetes. Genetic variants in the nicotinic acetylcholine receptors (nAChRs) 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.
- Received October 6, 2011.
- Accepted February 29, 2012.
- © 2012 by the American Diabetes Association.
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