A COMMON SUBSTITUTION (ASN291SER) IN LIPOPROTEIN-LIPASE IS ASSOCIATEDWITH INCREASED RISK OF ISCHEMIC-HEART-DISEASE

Lipoprotein lipase degrades triglycerides in plasma and as a byproduct produces HDL particles. Genetic variation in lipoprotein lipase may t herefore affect cardiovascular risk, We tested 9,214 men and women fro m a general population sample and 948 patients with ischemic heart dis ease for the Asn291Ser substitution in lipoprotein lipase. The allele frequency in the general population was 0.024 and 0.026 for women and men, respectively. In comparison with noncarriers, female heterozygous probands had increased plasma triglycerides (Delta = 0.23 mmol/liter) , while HDL cholesterol was reduced in both female and male carriers ( Delta = 0.18 mmol/liter and Delta = 0.11 mmol/liter, respectively), A similar phenotype was found in six homozygous carriers, On multiple lo gistic regression analysis, plasma triglycerides and HDL cholesterol w ere independent predictors of ischemic heart disease in both genders, On univariate analysis, odds ratios for ischemic heart disease in prob ands were 1.89 in women (95% CI: 1.19-3.01) and 0.90 in men (95% CI: 0 .62-1.31), and on multivariate analysis were 1.98 in women (35% CI: 1. 11-3.53) and 1.02 in men (95% CI: 0.65-1.60). This study demonstrates that a single common mutation in the lipoprotein lipase gene is associ ated with elevated plasma triglycerides and reduced HDL cholesterol le vels, whereby carriers, in particular women, seem to be predisposed to ischemic heart disease, It cannot be excluded, however, that male car riers of this substitution may represent a subset of low-HDL individua ls without raised triglycerides not predisposed to ischemic heart dise ase.