COMMON DNA POLYMORPHISMS AT THE LIPOPROTEIN-LIPASE GENE - ASSOCIATIONWITH SEVERITY OF CORONARY-ARTERY DISEASE AND DIABETES

Background DNA variants of the lipoprotein lipase gene are associated with changes in lipid metabolism similar to those in diabetes and may relate to the development of atherosclerotic lesions, particularly pre mature lesions. Methods and Results To determine whether lipoprotein l ipase gene variants are relevant to ongoing atherogenesis, we explored relationships between two common lipoprotein lipase gene polymorphic markers, Pvn II at intron 6 and HindIII at intron 8; the severity of c oronary artery disease (CAD); and lipid variables in 475 white patient s 65 years of age or younger. We assessed CAD severity as the number o f significantly stenosed (>50% luminal obstruction) major coronary art eries at angiography and by the Green Lane coronary score. We found a significant association between the Pvu II polymorphism and the number of significantly diseased vessels (P=.0099) and coronary score (P=.02 8), with the Pvu II(-) alleles associated with less severe disease. Th e HindIII polymorphism was not associated with severity but had an add itive effect with the Pvu II polymorphism. There was a close relations hip between the Pvu II(+/+) genotype and the presence of diabetes (P=. 0025), with an OR of 3.12 (95% CI, 1.30 to 7.49) compared with the Pvu II(-/-) genotype. The interaction between these polymorphisms and CAD severity (rather than occurrence) was independent of the levels of tr iglycerides and HDL cholesterol and of other lipid variables. There wa s also a dosage-dependent relationship between the Pvu II polymorphism and levels of triglyceride. The Pvu II(-) allele was associated with low levels and variances of triglycerides. Conclusions We conclude tha t the lipoprotein lipase Pvu II polymorphism is significantly associat ed with CAD severity and with type II diabetes in CAD patients, indepe ndent of changes in circulating lipid levels. These findings may be re levant to mechanisms mediating atherogenesis.