Lipoprotein lipase gene variants and risk of coronary disease: a quantitative analysis of population-based studies

The purpose of this study is to quantify the magnitude of the association between common variants in the lipoprotein lipase gene and coronary disease, based on published population-based studies. Fourteen studies, representing 15,708 subjects, report allelic distribution for lipoprotein lipase gene variants among coronary disease patients and control subjects. Patient outcomes included clinical coronary disease events and documented coronary disease based on angiography. Allele frequencies are estimated for disease and non-disease groups within each study. A 2 x 2 contingency table is used to compute individual study odds ratios and 95% confidence intervals, relating the presence of the rare allele to disease status. Mantel-Haenszel-stratified analysis of each allelic variant results in a summary odds ratio and 95% confidence interval for the association between each rare allele in the lipoprotein lipase gene and coronary disease. The lipoprotein lipase D9N allele has a summary odds ratio of 1.59 (95% confidence interval 1.03-2.55), indicating a 59% increase in risk of coronary disease for carriers with this allelic variant. The lipoprotein lipase N291S allele showed no association with coronary disease (summary odds ratio 0.93, 95% confidence interval 0.73-1.19). The summary odds ratio for lipoprotein lipase S447Ter allele is 0.81 (95% confidence interval 0.65-1.0), indicating a marginal negative association between this variant and coronary disease. The common lipoprotein lipase Pvu II polymorphism shows no relation to coronary disease (summary odds ratio 0.90, 95% confidence interval 0.80-1.01). The rare allele of the lipoprotein lipase HindIII polymorphism is negatively associated with coronary disease (summary odds ratio 0.84, 95% confidence interval 0.73-0.96). The lipoprotein lipase D9N allele is associated with high levels of triglyceride and low levels of high-density lipoprotein. Similar atherogenic lipid levels are observed in subjects with structural mutations lipoprotein lipase C188E and P207L. Carriers of the S447Ter allele have low levels of triglyceride. The lipoprotein, lipase gene variants which decrease lipoprotein lipase catalytic activity are associated with familial combined hyperlipidemia, but not the elevation of apolipoprotein B seen in this disorder. In conclusion, allelic variants in the lipoprotein lipase gene are associated with altered lipid levels and differential coronary disease risk.