EFFECTS OF APOE GENE POLYMORPHISM ON LP(A) CONCENTRATIONS DEPEND ON THE SIZE OF APO(A) - A STUDY OF 466 WHITE MEN

Polymorphisms in the genes for the low-density lipoprotein (LDL) recep tor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) l ipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprote in called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically d etermined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo( a) with triglyceride-rich lipoproteins differs with the size of apo(a) , and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible ef fect of genetic variation in the apoE and apoB genes on plasma Lp(a) c oncentrations in 466 white men with different apo(a) phenotypes. Overa ll there was no significant association between the common apoE polymo rphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations o f Lp(a) differed significantly among the apoE genotypes (P=0.05). Lp(a ) was highest in the apoE genotypes epsilon(2) epsilon(3) and epsilon( 3) epsilon(3) and lowest in genotype epsilon(3) epsilon(4), and the ap oE polymorphism was estimated to account for about 2.4% of the variati on in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was sig nificantly lower (P=0.04) in apoE genotype epsilon(2) epsilon(3) than in genotype epsilon(3) epsilon(3). Lp(a) concentrations did not differ among the XbaI (P=0.65) or SP 24/27 (P=0.26) polymorphisms of the apo B gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subject s with large-sized apo(a) isoforms (P<0.01), whereas no effect was see n in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on th e size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S 4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors.