The T allele of the hepatic lipase promoter variant C-480T is associated with increased easting lipids and HDL and increased preprandial and postprandial LpCIII : B - European Atherosclerosis Research Study (EARS) II

The common C-480T transition in the hepatic lipase (HL) promoter has been s hown to be associated with lower HL activity and increased high density lip oprotein (HDL) cholesterol. We examined the frequency and lipid association s of this HL polymorphism in 385 healthy, young (18- to 28-year-old) men wh ose fathers had had a premature myocardial infarction (designated cases) an d 405 age-matched controls. These individuals were participants in the Euro pean Atherosclerosis Research Study II postprandial trial, who had been rec ruited from II European countries in 4 regions (the Baltic; United Kingdom; and central and southern Europe). Overall, the frequency of the T allele w as 0.207 in controls and 0.244 in cases (P=0.08). The T allele was associat ed with higher fasting plasma total cholesterol (P<0.01), triglycerides (P< 0.01), and HDL cholesterol (P<0.01). The strongest association was found wi th apolipoprotein (apo) A-I concentration, which was 10% higher in individu als homozygous for the T allele compared with those homozygous for the C al lele (P<0.001). This polymorphism had no effect on the rise in plasma trigl yceride levels after a fatty meal. However, before and after the fat load w as ingested, levels of particles containing both apoC-III and apoB (LpC-III :B) were higher in carriers of the T allele, with homozygotes having 23% an d 27% higher levels preprandially and postprandially, respectively, than th ose homozygous for the C allele (P<0.05), Thus, our results demonstrate tha t the C-480T polymorphism in the HL promoter is associated with alterations in plasma lipids and lipoproteins and the accumulation of atherogenic LpC- III:B particles.