SINGLE NUCLEOTIDE POLYMORPHISMS IN THE APO(A) KRINGLE IV TYPE 8 DOMAIN AND ATHEROTHROMBOTIC SERUM LIPOPROTEIN (A) CONCENTRATION, IN A PORTUGUESE PEDIATRIC POPULATION

Abstract

Lipoprotein (a) (Lp[a]) is a complex of apolipoprotein (a) (apo[a]) and low-density lipoprotein (LDL), which is associated with atherothrombotic disease. Most of the interindividual variations in plasma levels of Lp(a) can be attributed to sequence differences linked to the apo(a) gene locus. Human apo(a) is a glycoprotein containing 10 different types of kringle (K) IV domains, which share a high degree of homology with plasminogen K IV. Recently, single nucleotide polymorphisms (SNP) in the exons and intronic sequences of the apo(a) K IV, have been investigated as to their effect on Lp(a) particle formation. The aim of this study was to investigate a possible link between some SNPs in the apo(a) K IV type 8 domain and atherothrombotic serum Lp(a) concentrations (Lp[a] >30 mg/dl). We studied 97 paediatric patients, 51 with serum Lp(a) concentration above and 46 with concentrations below 30 mg/dl. In all patients direct sequencing of the two exons and flanking intronic sequences of the apo(a) K IV type 8 domain was performed. Sequencing was carried out on the primary amplicons, using the respective forward and reverse primers, in independent sequencing reactions and subsequently resolved on an ABI Prism 310 GeneticAnalyser (Applied Biosystems, Foster City, USA). In this population, we found three SNPs, two in exon 1 (c.3888A > C and c.3955G > A) and one in intron 1 of the apo(a) K IV type 8 domain (c.3982+1G > A). The c.3888A > C polymorphism is most common with a heterozygosity frequency of 15.46%. The c.3955G > A and c.3982+1G > A polymorphisms were found in a frequency of 5.15% and 1.03%, respectively. No statistically significant difference was found in the genotype distribution between the two groups of patients, with Lp(a) above and below 30 mg/dl. Our results suggest that these SNPs in the apo(a) K IV type 8 domain are not directly associated with atherothrombotic serum Lp(a) concentrations in our population.