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Circulation. 1995;92:1765-1769

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(Circulation. 1995;92:1765-1769.)
© 1995 American Heart Association, Inc.


Articles

Polymorphisms in the Lipoprotein Lipase Gene and Their Associations With Plasma Lipid Concentrations in 40-Year-Old Danish Men

Christian Gerdes, MD; Lars Ulrik Gerdes, MD; Peter Steen Hansen, MD, PhD; Ole Faergeman, MD, DMSc

From the Department of Internal Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Aarhus, Denmark.

Correspondence to Dr C. Gerdes, Department of Internal Medicine and Cardiology A, Aarhus Amtssygehus University Hospital, Tage Hansensgade 2, DK-8000 Aarhus C, Denmark.

Background In some previous studies, HindIII and Pvu II restriction fragment length polymorphisms (RFLPs) in the lipoprotein lipase (LPL) gene were associated with coronary heart disease and plasma concentrations of HDL cholesterol and triglycerides. However, the populations studied were relatively small and heterogeneous in regard to age, sex, and ethnic background.

Methods and Results Associations of a HindIII (intron 8) and a Pvu II (intron 6) RFLP in the LPL gene with plasma concentrations of cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides were studied in 457 randomly selected 40-year-old Danish men. The HindIII and the Pvu II sites were in strong linkage disequilibrium. The frequencies of the H+ and P+ alleles (+ denotes presence of cutting site) were 0.717 and 0.464, respectively. In multivariate analysis, there was a clear gene dosage effect of the H+ allele on HDL. The lowest HDL cholesterol concentration was in the H+H+ group, the highest concentration was in the H-H- group, and the H+H- group had intermediate HDL concentrations (P=.03). There was a similar, but not statistically significant gene dosage effect on triglyceride concentrations, with the highest value seen in the H+H+ group. There were no other associations between LPL RFLPs and lipoprotein components. In males reporting family history of premature ischemic heart disease, the H+H+ genotype was overrepresented (odds ratio, 2.75; 95% confidence interval, 1.37 to 5.53).

Conclusions The results suggest that genetic variation in or near the LPL gene plays a role in interindividual differences in HDL cholesterol concentration and in risk of atherosclerosis and ischemic heart disease in men.


Key Words: lipoproteins • cholesterol • triglycerides • genes • coronary disease




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