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.
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.
authors.affiliation: University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Laura A
authors.initials: LA
authors.lastname: Beebe
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.forename: Lyle G
authors.initials: LG
authors.lastname: Best
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Henderson
authors.forename: Patricia
authors.initials: P
authors.lastname: Henderson
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011978:Receptors, Nicotinic