LIPOPROTEIN-LIPASE VARIANTS D9N AND N291S, ARE ASSOCIATED WITH INCREASED PLASMA TRIGLYCERIDE AND LOWER HIGH-DENSITY-LIPOPROTEIN CHOLESTEROLCONCENTRATIONS - STUDIES IN THE FASTING AND POSTPRANDIAL STATES - THEEUROPEAN ATHEROSCLEROSIS RESEARCH STUDIES

Background Variations at the DNA lever with moderate effects on bioche mical variables may be important for the occurrence of disease at the population level, if they are common. Two mutations in the LPL gene, N 9 and S291, are associated with variation in fasting plasma concentrat ions of HDL cholesterol (HDL-C) and triglycerides (TG). We investigate d whether these mutants were more frequent in offspring of cases with premature coronary disease and analyzed the effects on fasting plasma lipids and postprandial TG. Methods and Results Students with and with out paternal history of myocardial infarction (cases and control subje cts [controls]) were studied in the European Atherosclerosis Research Studies I and II (EARS-I and -II). Allelic frequencies for the N9 and S291 mutations did not differ between cases and control subjects. The N9 mutation was identified in 4.2% of all subjects in EARS-I, and carr iers had higher fasting TG levels (P<.001) than noncarriers. In an ora l fat tolerance test, there were no differences in postprandial TG bet ween carriers and noncarriers of the N9 allele. The S291 mutation was identified in 3.1% of all subjects in EARS-I, and carriers had lower f asting HDL-C levels (P<.005) than noncarriers. There was a significant interaction between S291 genotype and body mass index on fasting TG l evels (P<.01). In the cases, carriers of the S291 allele had higher TG levels 6 hours postprandially (P<.04) than did noncarriers. Conclusio ns The two LPL mutations are common and may predispose to elevated TG and decreased HDL-C concentrations, even in young subjects. In the cas e of the S291 mutation, this effect appears to be mediated via delayed postprandial TG clearance. Moreover, even moderate obesity potentiate s the TC-raising and HDL-lowering effects associated with the S291 all ele.