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Originally published as Genetics Published Articles Ahead of Print on November 1, 2004.

Genetics, Vol. 169, 1583-1587, March 2005, Copyright © 2005
doi:10.1534/genetics.104.037812

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Haplotype Analysis of the ß2 Adrenergic Receptor Gene and Risk of Myocardial Infarction in Humans

Robert Y. L. Zee*,1, Nancy R. Cook*, Rebecca Reynolds{dagger}, Suzanne Cheng{ddagger} and Paul M. Ridker*

* Center for Cardiovascular Disease Prevention, LeDucq Center for Molecular and Genetic Epidemiology and Harvard-Reynolds Center for Cardiovascular Research, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215
{dagger} Bayer HealthCare, East Walpole, Massachusetts 02032
{ddagger} Department of Human Genetics, Roche Molecular Systems, Alameda, California 94501

1 Corresponding author: Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, 900 Commonwealth Ave. East, Boston, MA 02215.
E-mail: rzee{at}rics.bwh.harvard.edu

Polymorphisms in the ß2 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 among cases and controls (, 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% C.I. 0.043–0.737, P = 0.017) and (non-G16-Q27)-T164 (odds ratio 1.235, 95% C.I. 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 ß2 adrenergic receptor gene was found to be associated with risk of myocardial infarction.




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