Combined analysis of six Lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease:: Cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study

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 epsilon 32 individuals and 2.4 ( CI, 1.4 - 4.1) among epsilon 43 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.