Renin-angiotensin system haplotypes and the risk of myocardial infarction and stroke in pharmacologically treated hypertensive patients.
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.
Marciante
Kristin D
KD
Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. marciant@u.washington.edu
Bis
Joshua C
JC
Rieder
Mark J
MJ
Reiner
Alexander P
AP
Lumley
Thomas
T
Monks
Stephanie A
SA
Kooperberg
Charles
C
Carlson
Christopher
C
Heckbert
Susan R
SR
Psaty
Bruce M
BM
D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology*; D014861:Washington / Q000453:epidemiology
D000959:Antihypertensive Agents; D044139:Receptor, Angiotensin, Type 2; D007703:Peptidyl-Dipeptidase A