Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men - The Copenhagen City Heart Study

The aim of this study was to test the hypothesis that the Asp9Asn substitut ion and the T(-93)-->G mutation in the promoter of the lipoprotein lipase g ene affect plasma lipid levels and thereby the risk of ischemic heart disea se (MD). We genotyped 9033 men and women from a general population sample a nd 940 patients with IHD. The frequency of both the G allele and the Asn9 a llele in the general population sample was approximate to 0.015 for both me n and women. These 2 mutations appeared together in 95% of carriers. The av erage triglyceride-raising effect associated with double heterozygosity for the T(-93)-->G mutation 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 r egression analysis allowing for age, the risk of IHD for double heterozygou s 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 all owed for, the risk of IHD for double heterozygous men and women was increas ed 70% (95% CI, 0% to 190%) and 20% (95% CI, -50% to 180%), respectively. O f the overall risk of IHD in men in the general population, the fraction at tributable to double heterozygosity was 3%, similar to the 5% attributable to diabetes mellitus. These results demonstrate that the Asp9Asn substituti on is in linkage disequilibrium with the T(-93)-->G mutation and that the d ouble-heterozygous carrier status is associated with elevated plasma trigly cerides and an increased risk of IHD in men.