Mutations in thelipoprotein lipaseGene Associated With Ischemic Heart Disease in Men

Publisher Website
Google Scholar
Abstract
—The aim of this study was to test the hypothesis that the Asp9Asn substitution and theT(−93)→Gmutation in the promoter of thelipoprotein lipasegene affect plasma lipid levels and thereby the risk of ischemic heart disease (IHD). We genotyped 9033 men and women from a general population sample and 940 patients with IHD. The frequency of both theGallele and the Asn9 allele in the general population sample was ≈0.015 for both men and women. These 2 mutations appeared together in 95% of carriers. The average triglyceride-raising effect associated with double heterozygosity for theT(−93)→Gmutation and the Asp9Asn substitution was 0.28 mmol/L (P=0.004) and 0.16 mmol/L (P=0.10) in men and women, respectively. On logistic regression analysis allowing for age, the risk of IHD for double heterozygous men and women was increased 90% (95% confidence interval [CI], 20% to 200%) and 30% (95% CI, −40% to 170%), respectively, compared with noncarriers. When, in addition, other conventional cardiovascular risk factors were allowed for, the risk of IHD for double heterozygous men and women was increased 70% (95% CI, 0% to 190%) and 20% (95% CI, −50% to 180%), respectively. Of the overall risk of IHD in men in the general population, the fraction attributable to double heterozygosity was 3%, similar to the 5% attributable to diabetes mellitus. These results demonstrate that the Asp9Asn substitution is in linkage disequilibrium with theT(−93)→Gmutation and that the double-heterozygous carrier status is associated with elevated plasma triglycerides and an increased risk of IHD in men.