Association of lipoproteid(a) with proprotein convertase subtilisin/kexin type 9 (PCSK9) in young males

Abstract

Aortic stenosis is most common valve disease in Europe, North America and Russia. Lipoproteid(a) [Lp(a)] is independent risk factor for coronary artery disease (CAD) and calcific aortic valve stenosis (CAVS). Two single-nucleotide polymorphism (SNP) in the LPA locus (rs10455872 and rs3798220) associated with an increase the level of Lp(a) and the development of CAVS. There have been no investigations about connection between phenotype аpоlipoprotein(а) (apo(a)) and polymorphism in the LPA loci with aortic valve stenosis in Russia till now.
Aim. To assess correlation between level and phenotype of Lp(a) with calcific aortic valve stenosis depending on coronary artery disease, and frequency of SNPs in the LPA loci rs10455872 and rs3798220 in patients with calcific aortic valve stenosis.
Materials and methods. The study included 249 subjects. They were divided into three groups: group 1, patients with CAD and CAVS (n=104), group 2 – patients with CAVS (n=62) and group 0 or control group – without CAVS and CAD (n=83). Concentrations of Lp(a), total cholesterol, low-density lipoprotein cholesterol and apo(a) phenotypes were measured in all subjects. The rs10455872 and rs3798220 genetic variants in the LPA were genotyped in patients with CAVS.
Results. Lp(a) level was maximal in group 1. Minor allele homozygotes for SNP rs10455872 (GG) and rs3798220 (CC) were not detected. The TC genotype was found in 10 (6%) patients and AG genotype in 18 (11%) patients with CAVS. Median [25; 75%] of Lp(a) level in patients with AG and TC genotype was 48,3 [35,8; 58,5] and 110,2 [82,2; 114,6] mg/dl, respectively, vs 15 [5,8; 41,8] and 15,3 [5,9; 43] mg/dl in subjects with normal AA and CC genotype. Maximum number of patients with low molecular weight
(LMW) apo(a) phenotypes were in group 1 than in others. LMW apo(a) phenotypes were observed for 6 (60%) patients with minor allele heterozygotes for SNP rs3798220 and 14 (77%) patients with minor allele heterozygotes for SNP rs10455872.
Conclusion. Elevated level of Lp(a) and LMW apo(a) phenotype associated with CHD in patients with CAVS. Correlation assessment between heterozygotes for SNP rs10455872 and rs3798220 with CAD and CAVS is not possible due to insufficient amount of patients with these mutations.