MedStar Authors catalog › Details for: Joint associations of 61 genetic variants in the nicotinic acetylcholine receptor genes with subclinical atherosclerosis in American Indians: a gene-family analysis.
Citation: Circulation. Cardiovascular Genetics. 6(1):89-96, 2013 Feb..Journal: Circulation.ISSN: 1942-3268.Full author list: Best LG; Cole SA; Devereux RB; Haack K; Howard BV; Lee ET; Roman MJ; Yang J; Zhang Y; Zhao J; Zhu Y.UI/PMID: 23264444.Subject(s): *Atherosclerosis/ge [Genetics] | *Genetic Variation | *Indians, North American/ge [Genetics] | *Multigene Family | *Receptors, Nicotinic/ge [Genetics] | Adult | Atherosclerosis/pp [Physiopathology] | Carotid Intima-Media Thickness | Female | Genetic Predisposition to Disease | Humans | Male | Middle Aged | Pedigree | Polymorphism, Single Nucleotide | Prospective Studies | Risk FactorsInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal Article | Multicenter Study | Research Support, N.I.H., ExtramuralOnline resources: Click here to access onlineDigital Object Identifier: http://dx.doi.org/10.1161/CIRCGENETICS.112.963967 (Click here)Abbreviated citation: Circ Cardiovasc Genet. 6(1):89-96, 2013 Feb.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.Abstract: 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.Abstract: METHODS AND 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.