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Am J Epidemiol 2003; 158:836-843.
Copyright © 2003 by Johns Hopkins Bloomberg School of Public Health


ORIGINAL CONTRIBUTIONS

Effects of the Hepatic Lipase Gene and Physical Activity on Coronary Heart Disease Risk

John E. Hokanson1 , M. Ilyas Kamboh2, Sharon Scarboro1, Robert H. Eckel3 and Richard F. Hamman1

1 Department of Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, CO.
2 Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
3 Department of Medicine, University of Colorado Health Sciences Center, Denver, CO.

There are environmental determinants and genetic susceptibility to coronary heart disease (CHD); however, identifying factors that modify genetic risk has been difficult. Evidence suggests that a common polymorphism in the hepatic lipase gene (LIPC-480C>T) may be related to susceptibility to CHD and that physical activity is a behavioral factor associated with CHD. This population-based prospective study in the San Luis Valley of Colorado investigated the role of the LIPC-480C>T polymorphism in predicting clinical CHD and the modifying effect of physical activity. Hispanics and non-Hispanic Whites (n = 966) were followed for 14 years (1984–1998); 91 CHD events occurred. The LIPC-480 TT genotype predicted an increase in CHD in both ethnic groups, and physical activity altered this relation. In the full cohort, the rate of CHD was significantly elevated among subjects with the high-risk genotype and normal levels of physical activity (hazard ratio = 2.58, 95% confidence interval: 1.39, 4.77) but was not elevated among those with the high-risk genotype who participated in vigorous physical activity (hazard ratio = 0.52, 95% confidence interval: 0.12, 2.19) (reference group: LIPC-480 CC/CT, normal physical activity). Thus, in this prospective cohort study, the LIPC-480 TT genotype increased susceptibility to CHD only in those subjects with normal levels of physical activity, not in those with the high-risk genotype who were vigorously active.

cohort studies; coronary disease; genetic predisposition to disease; polymorphism (genetics); risk factors

Abbreviations: Abbreviations: CHD, coronary heart disease; HDL, high density lipoprotein; LDL, low density lipoprotein; SD, standard deviation.


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