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

Diabetes. 2012 Jul;61(7):1888-94. doi: 10.2337/db11-1393. Epub 2012 May 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Association Studies / statistics & numerical data
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Humans
  • Indians, North American / genetics*
  • Insulin / blood
  • Insulin Resistance / genetics*
  • Male
  • Middle Aged
  • Pedigree
  • Polymorphism, Single Nucleotide
  • Receptors, Nicotinic / genetics*
  • Smoking / epidemiology
  • Smoking / genetics
  • Young Adult

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Nicotinic