A Gene-Family Analysis of 61 Genetic Variants in the Nicotinic Acetylcholine Receptor Genes for Insulin Resistance and Type 2 Diabetes in American Indians

  1. Jinying Zhao1
  1. 1University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  2. 2Texas Biomedical Research Institute, San Antonio, Texas
  3. 3Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
  4. 4MedStar Health Research Institute, Hyattsville, Maryland; the Georgetown-Howard Universities Center for Clinical and Translational Sciences, Washington, District of Columbia
  5. 5Missouri Breaks Industries Research Inc, Timber Lake, South Dakota
  6. 6New York Hospital-Cornell Medical Center, New York, New York
  7. 7Black Hills Center for American Indian Health, Rapid City, South Dakota
  1. Corresponding author: Jinying Zhao, jinying-zhao{at}


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.


  • Received October 6, 2011.
  • Accepted February 29, 2012.

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  1. Diabetes vol. 61 no. 7 1888-1894
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