DNA POLYMORPHISMS AT THE LIPOPROTEIN-LIPASE GENE AND THEIR ASSOCIATION WITH QUANTITATIVE VARIATION IN PLASMA HIGH-DENSITY-LIPOPROTEINS AND TRIACYLGLYCERIDES

Lipoprotein lipase (LPL) plays a critical role in the metabolism of li poproteins because this enzyme hydrolyzes the triacylglycerides in chy lomicrons and very low density lipoproteins. This process influences t he production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LP L qualifies as a candidate gene for understanding lipid metabolic diso rders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivoc al results to date. To help clarify this issue, we investigated 144 ou twardly healthy male Mediterranean migrants (from Italy and Greece), a ge between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the followi ng lipid and lipoprotein phenotypes: total plasma cholesterol, low-den sity lipoprotein (LDL), high-density lipoprotein (HDL), and triacylgly cerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism a t the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvuII polymorp hism, however, showed no association with any lipid. Kruskal-Wallis te sts confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertri acylglyceridemia and normolipidemics, a significant difference was obs erved in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were mo st at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII p olymorphism on both LDL cholesterol and total cholesterol levels.