Abstract

Lipoprotein(a) (Lp(a)) is an independent, genetically regulated cardiovascular risk factor. Lp(a) plasma levels are largely determined by the apolipoprotein(a) (apo(a)) component, and differ across ethnicity. Although a number of polymorphisms in the apo(a) gene have been identified, apo(a) genetic regulation is not fully understood. To study the relation between apo(a) gene variants, we constructed haplotypes and assessed linkage equilibrium in African Americans and Caucasians for three widely studied apo(a) gene polymorphisms (apo(a) size, +93 C/T and pentanucleotide repeat region (PNR)). Apo(a) size allele frequency distributions were different across ethnicity (p<0.01). For African Americans, PNR frequencies were similar across apo(a) sizes, suggesting linkage equilibrium. For Caucasians, the PNR and the PNR-C/T haplotype frequencies differed for large and small apo(a), with the T and PNR 9 alleles associated with large apo(a) size (p<0.0002); also, the PNR 9 allele was more common on a T allele, while PNR 8 was more common on a C allele. On a C allele background, small PNR alleles were more common and the PNR 10 allele less common among African Americans than Caucasians (p<0.001). The ethnic difference in apo(a) size distribution remained controlling for C/T and PNR alleles (p=0.023). In conclusion, allele and haplotype frequencies and the nature of the linkage disequilibrium differed between African Americans and Caucasians at three apo(a) gene polymorphisms.