Mild association between the A/G polymorphism in the promoter of the apolipoprotein A-I gene and apolipoprotein A-I levels: a meta-analysis.

A polymorphism caused by a G-to-A substitution in the promoter area (-75 bp) of the apolipoprotein AI (apo A-I) bene is common in the general population. Several studies have investigated its association with apo A-I levels, but the results were conflicting. Here, we undertook meta-analyses to increase the statistical power to further detect this association. Meta-analyses were first performed for each gender and then on the combined data. The overall sample in this meta-analysis included over 3,000 healthy individuals. Results from healthy individuals suggest that the rare allele A is associated with mildly increased apo A-I levels by about 5 mg/dl (95% CI 2.84 - 6.94). This association is weaker among healthy females than males. The present study cannot determine whether this small but significant association was due to a small genetic effect of the A/G polymorphism, or whether the A/G polymorphism is in linkage disequilibrium with a true mutant allele at a quantitative trait locus controlling apo A-I levels. Although smoking status may interact with genotypes, only three studies investigated this interaction and thus no conclusion could be drawn in this regard.