Effects of apolipoprotein A‐I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels

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Abstract
The present authors investigated the individual and combined associations of the apolipoprotein (apo) A‐I −75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position −75 bp (G→A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C→T and G→A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low‐density lipoprotein cholesterol (LDL‐C) (P = 0.018) and TC:high‐densisty lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the −75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A‐I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/– subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A‐I −75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/–) had significantly higher TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A‐I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/– haplotype having the highest values compared to other genotype combinations. In conclusion, the −75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL‐C in women, while the +83 bp polymorphism seems to affect the apo A‐I levels in men, and the plasma cholesterol levels in both genders.

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