POLYMORPHISMS IN THE LIPOPROTEIN-LIPASE GENE AND THEIR ASSOCIATIONS WITH PLASMA-LIPID CONCENTRATIONS IN 40-YEAR-OLD DANISH MEN

Background In some previous studies, HindIII and Pvu II restriction fr agment length polymorphisms (RFLPs) in the lipoprotein lipase (LPL) ge ne were associated with coronary heart disease and plasma concentratio ns of HDL cholesterol and triglycerides. However, the populations stud ied were relatively small and heterogeneous in regard to age, sex, and ethnic background. Methods and Results Associations of a HindIII (int ron 8) and a Pvu II (intron 6) RFLP in the LPL gene with plasma concen trations of cholesterol, HDL cholesterol, non-HDL cholesterol, and tri glycerides were studied in 457 randomly selected 40-year-old Danish me n. The HindIII and the Pvu II sites were in strong linkage disequilibr ium. The frequencies of the H+ and P+ alleles (+ denotes presence of c utting site) were 0.717 and 0.464, respectively. In multivariate analy sis, 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 highe st concentration was in the H-H- group, and the H+H- group had interme diate HDL concentrations (P=.03). There was a similar, but not statist ically significant gene dosage effect on triglyceride concentrations, with the highest value seen in the H+H+ group. There were no other ass ociations between LPL RFLPs and lipoprotein components. In males repor ting family history of premature ischemic heart disease, the H+H+ geno type was overrepresented (odds ratio, 2.75; 95% confidence interval, 1 .37 to 5.53). Conclusions The results suggest that genetic variation i n or near the LPL gene plays a role in interindividual differences in HDL cholesterol concentration and in risk of atherosclerosis and ische mic heart disease in men.