American Journal of Epidemiology Advance Access originally published online on May 22, 2007
American Journal of Epidemiology 2007 166(1):19-27; doi:10.1093/aje/kwm059
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ORIGINAL CONTRIBUTIONS |
Renin-Angiotensin System Haplotypes and the Risk of Myocardial Infarction and Stroke in Pharmacologically Treated Hypertensive Patients
1 Cardiovascular Health Research Unit, University of Washington, Seattle, WA
2 Department of Medicine, University of Washington, Seattle, WA
3 Department of Epidemiology, University of Washington, Seattle, WA
4 Department of Genome Sciences, University of Washington, Seattle, WA
5 Department of Biostatistics, University of Washington, Seattle, WA
6 Department of Statistics, Oklahoma State University, Stillwater, OK
7 Fred Hutchinson Cancer Research Center, Seattle, WA
8 Department of Health Services, University of Washington, Seattle, WA
Correspondence to Dr. Kristin D. Marciante, Cardiovascular Health Research Unit, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101 (e-mail: marciant{at}u.washington.edu).
Received for publication June 14, 2006. Accepted for publication January 16, 2007.
The products of the renin-angiotensin system (RAS) play an important role in the pathogenesis of cardiovascular disease. Studies examining RAS gene variants and cardiovascular disease have focused on single-nucleotide polymorphisms (SNPs) rather than haplotypes, which better characterize the patterns of genetic variation. The authors conducted a population-based, case-control study at Group Health (Seattle, Washington) between 1995 and 1999 to determine whether common haplotypes in the angiotensinogen gene (AGT), the renin gene, the angiotensin-converting enzyme gene, and the angiotensin II receptor type 1 and receptor type 2 genes were associated with the risk of myocardial infarction and stroke among pharmacologically treated hypertensive patients. SNP discovery was done using 23 European-origin samples. Thirty tagSNPs (the minimum sets of SNPs that capture most of the haplotype diversity within a block) were genotyped in cases and controls. Haplotypes were inferred using the program PHASE (http://www.stat.washington.edu/stephens/software.html). The authors used weighted logistic regression to estimate associations and conducted a permutation test to estimate the probability of a chance finding. AGT haplotype B was associated with the risk of myocardial infarction (odds ratio = 1.58, 95% confidence interval: 1.06, 2.35); however, results were not statistically significant given the number of tests performed (permutation p = 0.17). In this case-control study, RAS gene haplotypes were not significantly associated with increased risks of myocardial infarction or stroke.
cerebrovascular accident; genetics; hypertension; myocardial infarction
Abbreviations: CI, confidence interval; OR, odds ratio; RAS, renin-angiotensin system; SNP, single-nucleotide polymorphism