Effects of apolipoprotein A gene polymorphisms on lipoprotein (a) concentrations in Japanese

1. Elevated plasma lipoprotein (a) (Lp(a)) concentrations have been correla ted with an increased risk of premature cardiovascular disease. The plasma Lp(a) concentration is quantitatively heritable and the apolipoprotein (Apo ) A gene is known as a major locus-determining Lp(a) concentration. 2. The aim of the present study was to evaluate the genetic effect of polym orphisms in the 5'-untranslated region (UTR) of the ApoA gene on plasma con centrations of Lp(a), 3. We analysed two sequence variations in the 5'-UTR, a pentanucleotide rep eat (PNR) polymorphism and haplotypes composed of three single base substit utions, in 325 Japanese subjects. The ApoA size polymorphism was also analy sed by western blotting. 4. The plasma Lp(a) concentration was inversely correlated with the size of the ApoA molecule. Both PNR and the haplotype polymorphisms had significan t effects on serum Lp(a) concentrations (P = 0.001 and 0.004, respectively) when the effects were evaluated by ANCOVA using the ApoA size polymorphism as a covariate. 5. When a stratified subpopulation with a larger ApoA size was analysed, bo th variations influenced or tended to influence the serum Lp(a) concentrati on, confirming the results of the ANCOVA, 6. Pentanucleotide repeat showed a tight linkage disequilibrium with the ha plotypes, This disequilibrium may account for the apparent effects of PNR o n Lp(a) concentrations.