The association of the apolipoprotein E gene promoter polymorphisms and haplotypes with serum lipid and lipoprotein concentrations

Background: Apolipoprotein E (ApoE) is known to modulate lipoprotein transport and metabolism. The common APOE 2/ 3/ 4 polymorphism explains part of the variation in plasma cholesterol levels. Polymorphisms of the APOE gene regulatory region are suggested to be involved in explaining variation of lipoprotein levels within the APOE 2/ 3/ 4 genotypes. Objectives: To study the associations of the APOE gene promoter polymorphisms −219G/T and +113G/C and their haplotypes with serum lipid and lipoprotein concentrations, especially within the most common APOE 3/ 3 genotype group. Subjects and methods: From 219 middle-aged Finnish men, APOE genotypes were determined and haplotypes estimated. Plasma lipoproteins were isolated by ultracentrifugation and their lipids were measured. Results: The studied APOE promoter polymorphisms and haplotypes associated with certain lipid variables independently of the APOE 2/ 3/ 4 genotype. Within the APOE 3/ 3 group, both −219G/G and +113G/G genotypes associated statistically significantly with higher levels of very low-density lipoprotein (VLDL) cholesterol, apoB and triglycerides, and tended to associate with lower HDL-cholesterol concentrations than the other genotypes. Compared with the −219T/+113C/ 3 haplotype, the more common −219G/+113G/ 3 haplotype was found more frequently among the group having high (over median) VLDL-cholesterol and triglyceride concentrations (OR 2.6, p < 0.001 and OR=2.1, p = 0.009, respectively). Conclusions: In addition to the APOE 2/ 3/ 4 polymorphism, the promoter polymorphisms −219G/T and +113G/C as well as their haplotype modulate lipid and lipoprotein concentrations in middle-aged Finnish men.