The effect of six polymorphisms in the Apolipoprotein B gene on parameters of lipid metabolism in a Danish population.

Abstract

Lipoproteins are vehicles for the distribution of plasma lipids and polymorphisms in the genes for apolipoproteins could influence the amount of lipid in plasma. We examined the effect of six single nucleotide polymorphisms in codons 71, 591, 2488, 2712, 3611, and 4154 of the apolipoprotein B gene on fasting levels of triglyceride, VLDL-, LDL-, HDL- and total cholesterol and on body mass index (BMI) in a cohort of 2656 Danes aged 40-70 years using a linear model correcting for the effects of gender, age, BMI, smoking, alcohol consumption and physical activity. The codon 2488 polymorphism was the most influential of the tested polymorphisms, significantly influencing triglyceride (P = 0.002), LDL-cholesterol (P < or = 0.0004), VLDL-cholesterol (P = 0.006) and total cholesterol (P = 0.0001). The codon 2712 polymorphism had an impact on triglyceride (P = 0.007) and VLDL-cholesterol (P = 0.001), while the codon 71 polymorphism influenced LDL- and total cholesterol (P = 0.04 and P = 0.02, respectively). An interaction between smoking and codon 591 (P = 0.03) and smoking and codon 3611 (P = 0.02) on BMI was observed, as well as modest interactions between codon 3611 and codons 2488 and 2712 on lipid parameters. All polymorphisms were in close linkage disequilibrium. The population was not in Hardy-Weinberg equilibrium in four of the six polymorphisms but the lack of equilibrium was restricted mainly to the 60-year olds.