POLYMORPHISMS IN THE APOLIPOPROTEIN(A) GENE AND THEIR RELATIONSHIP TOALLELE SIZE AND PLASMA LIPOPROTEIN(A) CONCENTRATION

Genotypes at five previously described polymorphic sites at the apolip oprotein(a) gene locus have been determined for the members of 27 fami lies as well as for unrelated white Caucasian and Asian-Indian subject s, and their relationship with isoform size and plasma lipoprotein(a) concentrations investigated, There was strong linkage disequilibrium b etween sites at the 5'-region of the gene and also between this region and a site in the coding sequence for Kringle 4-37 on the other side of the polymorphic Kringle 4 repeat region, There was no evidence that changes at any of the sites had any direct effect upon lipoprotein(a) concentration. However, certain haplotypes were present almost exclus ively on apolipoprotein(a) alleles within a restricted range of sizes and associated lipoprotein(a) concentrations. After correcting for the effect of allele size, there were clear differences between the lipop rotein(a) concentrations associated with alleles of different haplotyp es, suggesting that there may be genetically distinct groups of apolip oprotein alleles of different size and different levels of expression, Factors that regulate expression apparently exchange at a rate simila r to the rate of change of Kringle 4 repeat number.