The T Allele of the Hepatic Lipase Promoter Variant C−480T Is Associated With Increased Fasting Lipids and HDL and Increased Preprandial and Postprandial LpCIII:B

Abstract

Abstract-The common CϪ480T transition in the hepatic lipase (HL) promoter has been shown to be associated with lower HL activity and increased high density lipoprotein (HDL) cholesterol. We examined the frequency and lipid associations of this HL polymorphism in 385 healthy, young (18-to 28-year-old) men whose fathers had had a premature myocardial infarction (designated cases) and 405 age-matched controls. These individuals were participants in the European Atherosclerosis Research Study II postprandial trial, who had been recruited from 11 European countries in 4 regions (the Baltic; United Kingdom; and central and southern Europe). Overall, the frequency of the T allele was 0.207 in controls and 0.244 in cases (Pϭ0.08). The T allele was associated with higher fasting plasma total cholesterol (PϽ0.01), triglycerides (PϽ0.01), and HDL cholesterol (PϽ0.01). The strongest association was found with apolipoprotein (apo) A-I concentration, which was 10% higher in individuals homozygous for the T allele compared with those homozygous for the C allele (PϽ0.001). This polymorphism had no effect on the rise in plasma triglyceride levels after a fatty meal. However, before and after the fat load was 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% and 27% higher levels preprandially and postprandially, respectively, than those homozygous for the C allele (PϽ0.05).

Associations between HDL-cholesterol and polymorphisms in hepatic lipase and lipoprotein lipase genes are modified by dietary fat intake in African American and White adults

“…In the current study, adjustment for carbohydrate intake in multivariable models had nominal effects; however, carbohydrate and total fat showed a correlation of -0.68 (adjusted for total energy). Finally, neither CETP nor LIPC were in Hardy-Weinberg equilibrium in Whites, although the allele frequencies were similar to those reported in other Caucasian populations (10,19,50), and the blind duplicate data were consistent. Nevertheless, it is possible that our findings were biased by the greater number of wild type and minor allele homozygotes than expected for these two genes (51).…”

Age-Related Effects of Genetic Variation on Lipid Levels: The Columbia University BioMarkers Study

“…Analyses were conducted using Intercooled STATA version 6 (Stata Corp, College Station, TX). From initial analyses and in agreement with Jansen et al, 36 lipid values for carriers of the rare alleles for the HL and the APOC3 polymorphisms were similar, and for all subsequent analyses heterozygotes were combined with rare homozygotes. To determine the allelic association between the 2 APOC3 variants, we calculated linkage disequilibrium (⌬) using the method of Chakravarti et al 38 For LPL, the frequency of the rare allele was low and rare allele carriers were pooled for all analyses.…”

“…Other studies have shown an association in adults of the HL Ϫ480T allele with higher HDL cholesterol levels. 15,17,18,36 We found frequency differences for the HL Ϫ480CϾT and APOC3 Ϫ455CϾT and 482CϾT polymorphisms between Hispanic and non-Hispanic whites, with the Hispanics having higher frequencies of the rare allele in both genes. We previously identified a highly significant frequency difference of the APOC3 Ϫ482CϾT between whites, Asians from the Indian subcontinent, and Africans, all living in South London, suggesting that this polymorphism shows a high degree of ethnic variation.…”

“…In both the children and the adults, overall, the Ϫ480T allele was associated with higher TG levels, confirming previous results. 36 When obesity is taken into account in the children, the partitioning of this effect is such that among children in the higher tertiles of skinfolds, in whom TG levels are higher (because obesity and TG are positively correlated), the Ϫ480T allele was associated with higher HDL levels. Thus, our findings suggest that at the higher TG level, HL Ϫ480T allele is having a larger effect on HDL raising.…”

Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population

“…Thus, HL promoter variation had significant effects on the variability of HDL-C levels, predominantly through the Ϫ514C/C genotype decreasing HDL-C levels in the Japanese population. HL promoter genotypes have been well characterized in Caucasian populations (Guerra et al 1997;Nie et al 1998;Grundy et al 1999;Murtomaki et al 1997;Jansen et al 1997;Tahvanainen et al 1998;Shohet et al 1999;Jansen et al 1999). However, there are a few reports on other populations Zambon et al 1998).…”