title: Joint associations of 61 genetic variants in the nicotinic acetylcholine receptor genes with subclinical atherosclerosis in American Indians: a gene-family analysis.
abstract: BACKGROUND
  Atherosclerosis is the underlying cause of cardiovascular disease, the leading cause of morbidity and mortality in all American populations, including American Indians. Genetic factors play an important role in the pathogenesis of atherosclerosis. Although a single-nucleotide polymorphism (SNP) may explain only a small portion of variability in disease, the joint effect of multiple variants in a pathway on disease susceptibility could be large.
  
  
  RESULTS
  Using a gene-family analysis, we investigated the joint associations of 61 tag SNPs in 7 nicotinic acetylcholine receptor genes with subclinical atherosclerosis, as measured by carotid intima-media thickness and plaque score, in 3665 American Indians from 94 families recruited by the Strong Heart Family Study (SHFS). Although multiple SNPs showed marginal association with intima-media thickness and plaque score individually, only a few survived adjustments for multiple testing. However, simultaneously modeling of the joint effect of all 61 SNPs in 7 nicotinic acetylcholine receptor genes revealed significant association of the nicotinic acetylcholine receptor gene family with both intima-media thickness and plaque score independent of known coronary risk factors.
  
  
  CONCLUSIONS
  Genetic variants in the nicotinic acetylcholine receptor gene family jointly contribute to subclinical atherosclerosis in American Indians who participated in the SHFS. These variants may influence the susceptibility of atherosclerosis through pathways other than cigarette smoking per se.
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Lee
authors.affiliation: Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.affiliation: Texas Biomedical Research Institute, San Antonio, TX.
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.affiliation: Missouri Breaks Industries Research Inc., Timber Lake, SD.
authors.forename: Lyle G
authors.initials: LG
authors.lastname: Best
authors.affiliation: The New York Hospital-Cornell Medical Center, New York, NY.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Devereux
authors.affiliation: The New York Hospital-Cornell Medical Center, New York, NY.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Roman
authors.affiliation: MedStar Health Research Institute Hyattsville, MD & Georgetown and Howard Universities Centers for Translational Sciences, Washington DC.
authors.forename: Barbara V
authors.initials: BV
authors.lastname: Howard
authors.affiliation: Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors.forename: Jinying
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011978:Receptors, Nicotinic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D011978:Receptors, Nicotinic