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Posts Tagged ‘Ying Zhang’


Nicotinic Acetylcholine Receptor Genes with Subclinical Atherosclerosis in American Indians: Genetic Variants Study and Gene-Family Analysis

Reporter: Aviva Lev-Ari, PhD, RN

Joint Associations of 61 Genetic Variants in the Nicotinic Acetylcholine Receptor Genes with Subclinical Atherosclerosis in American Indians – A Gene-Family Analysis

Jingyun Yang, PhD*Yun Zhu, MS*Elisa T. Lee, PhD, Ying Zhang, PhD, Shelley A. Cole, PhD, Karin Haack, PhD, Lyle G. Best, BS MD, Richard B. Devereux, MD, Mary J. Roman, MD, Barbara V. Howard, PhD and Jinying Zhao, MD, PhD

Author Affiliations

From the Tulane University School of Public Health and Tropical Medicine, New Orleans, LA (J.Y., Y. Zhu, J.Z.); Center for American Indian Health Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK (E.T.L., Y. Zhang); Texas Biomedical Research Institute, San Antonio, TX (S.A.C., K.H.); Missouri Breaks Industries Research Inc, Timber Lake, SD (L.G.B.); The New York Hospital-Cornell Medical Center, New York, NY (R.B.D., M.J.R.); MedStar Health Research Institute, Hyattsville, MD (B.V.H.); and Georgetown and Howard Universities Centers for Translational Sciences, Washington, DC (B.V.H.).

Correspondence to Jinying Zhao, MD, PhD, Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St, SL18, New Orleans, LA 70112. E-mail jzhao5@tulane.edu

* These authors contributed equally to this work.

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.

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.

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.

SOURCE:

Circulation: Cardiovascular Genetics.2013; 6: 89-96

Published online before print December 22, 2012,

doi: 10.1161/ CIRCGENETICS.112.963967

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