Search

Context: Hepatic lipase influences metabolism of high-density lipoprotein (HDL), a risk factor for ischemic cardiovascular disease (ICD: ischemic heart disease and ischemic cerebrovascular disease)., Objective: We tested the hypothesis that genetic variation in the hepatic lipase genetic variants V73M, N193S, S267F, L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD., Design: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747 of whom had incident ICD during 28 yr of follow-up. For the case-control studies, 2110 ischemic heart disease patients vs. 4899 controls and 769 ischemic cerebrovascular disease patients vs. 2836 controls, respectively, were genotyped. Follow-up was 100% complete., Results: HDL cholesterol was higher by 0.21 mmol/liter in S267F heterozygotes, by 0.06 mmol/liter in -480c>t heterozygotes, and by 0.13 mmol/liter in -480c>t homozygotes, as compared with noncarriers. These HDL increases theoretically predicted hazard ratios for ICD of 0.87 [95% confidence interval (CI) 0.84-0.90], 0.96 (95% CI 0.95-0.97), and 0.91 (95% CI 0.89-0.94), respectively; this calculation assumes that genetically elevated HDL levels confer decreased risk similar to common HDL elevations. In contrast, when all cases and controls were combined, the observed odds ratios for ICD for these three genetic variants vs. noncarriers were 1.19 (0.76-1.88), 1.04 (0.96-1.13), and 1.08 (0.89-1.30), respectively. Hazard/odds ratios for ICD in carriers vs. noncarriers of the four remaining hepatic lipase genetic variants did not differ consistently from 1.0., Conclusion: Hepatic lipase genetic variants with elevated levels of HDL cholesterol did not associate with risk of ICD.

Context: Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)., Objective: The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein lipase genotypes on triglycerides, HDL, and IHD., Design: The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively., Setting: The study was performed in the Danish general population (the Copenhagen City Heart Study)., Participants: IHD was angina pectoris or myocardial infarction., Main Outcome Measures: Triglycerides, HDL, and IHD were the main outcome measures., Results: Cross-sectionally, triglycerides varied by genotype with 1.27 mmol/liter in women and 1.22 mmol/liter in men. HDL cholesterol varied by genotype with 0.49 mmol/liter in women and 0.60 mmol/liter in men. Prospectively, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had a hazard ratio for IHD of 1.6 [95% confidence interval (CI), 1.2-2.3]; 291Ser and 447Ter did not change IHD risk. In the case-control study, combining the cohorts of IHD patients, 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers had an odds ratio for IHD of 1.5 (CI, 1.2-2.1). 291Ser and 447Ter did not change IHD risk. Stratified for apolipoprotein E genotype, the odds ratios for IHD in 9Asn (with -93G) heterozygotes and homozygotes combined vs. noncarriers were 2.6 (CI, 1.2-5.5) among epsilon32 individuals and 2.4 (CI, 1.4-4.1) among epsilon43 individuals., Conclusions: Genetic variation in lipoprotein lipase is associated with differences in plasma triglycerides greater than 1 mmol/liter and differences in HDL cholesterol greater than 0.5 mmol/liter. A 1.6-fold risk of IHD in 9Asn (with -93G) heterozygotes and homozygotes combined is influenced by apolipoprotein E genotype.