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doi:10.1534/genetics.104.037812
A more recent version of this article appeared on March 1, 2005.
REGULAR RESEARCH PAPERS |
Haplotype Analysis of the Beta-2 Adrenergic Receptor Gene and Risk of Myocardial Infarction
Robert Y. L. Zee 1*, Nancy R. Cook 1, Rebecca Reynolds 2, Suzanne Cheng 3 and Paul M. Ridker 1
1 Division of Preventive Medicine, Brigham & Women's Hospital, Harvard Medical School
2 Bayer HealthCare, E. Walpole, MA
3 Roche Molecular Systems, Alameda CA
* To whom correspondence should be addressed. E-mail: rzee{at}rics.bwh.harvard.edu.
Submitted on October 22, 2004
Revised on October 30, 2004
Accepted on 30 October 2004
Polymorphisms in the beta-2 adrenergic receptor (ADRB2), in particular G16R, Q27E and T164I, have been implicated in the pathogenesis of cardiovascular and metabolic phenotypes. However, no prospective, genetic-epidemiological data are available on the risk of cardiovascular disease associated with these variants. Using DNA samples collected at baseline in a prospective cohort of 14,916 initially healthy American men, we evaluated the G16R, Q27E, and T164I polymorphisms among 523 individuals who subsequently developed myocardial infarction and among 2092 individuals who remained free of reported cardiovascular events during follow-up. The haplotype-frequency distribution was significantly different between cases and controls (c27df=20.92, p=0.0039). Haplotype-based logistic regression, adjusting for age, smoking and randomized treatment group, indicated that G16-Q27-I164 (odds ratio=0.178, 95%CI=0.043-0.737, p=0.017), and (non-G16-Q27)-T164 (odds ratio=1.235, 95%CI=1.031-1.480, p=0.022) haplotypes were significantly associated with altered risk of myocardial infarction. These findings remained after further adjustment for BMI, history of hypertension, and presence or absence of diabetes. In conclusion, variation in haplotype frequencies for the beta-2 adrenergic receptor gene may be associated with risk of myocardial infarction.
Key Words: ADRB2, MI, association, genetics, risk factor
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