ASSOCIATION OF POLYMORPHISM IN PCSK9 GENE WITH LIPID PR OFILE IN RUSSIAN POPULATION

Background and aims: mutations in LDLR, APOB, PCSK9 genes determine the development of autosomal dominant forms of familial hypercholesterolemia. The PCSK9 gene encodes an enzyme involved in the metabolism of low density lipoprotein (LDL) by post-transcriptional regulation of the LDL receptors. Purpose: to perform analysis of PCSK9 rs562556, rs11591147 in Russian population and the population sub-samples of persons with hyper- and hypocholesterolemia; to investigate the PCSK9 protein association with rs562556, rs11591147 the PCSK9 gene at the population level. Materials and methods: genotyping rs562556 in the PCSK9 was carried out in a population and in the subgroup with hypercholesterolemia; genotyping rs11591147 was carried out in a population and in the subgroups with normal and low level of total cholesterol. Subgroups were included in the analyses in the HAPIEE project framework (9360 participants, 45-69 years old, 50% men). Blood lipid levels were determined using standard enzymatic assays. Genotyping of the PCSK9 rs11591147 was performed using PCR-RFLP and then confirmed by direct sequencing. Genotyping of the PCSK9 rs562556 was performed by RT-PCR using sets of "Syntol" (Russia). Results:Analysis of rs562556 association with lipid profile and PCSK9 protein blood levels showed these polymorphisms do not significantly contribute to forming hypercholesterolemia in Caucasian populations of Western Siberia."Loss of function" mutation R46L (PCSK9 rs11591147) association with total cholesterol levels in the group with normal and low levels of total cholesterol was revealed. Conclusion: The PCSK9 rs562556, rs11591147 alleles and genotypes frequency in the population and in the population subgroups with hyper- and hypocholesterolemia were determinedfor the first time in Russia. The Caucasian population of West Siberia does not significantly differ from populations of Europe by alleles and genotypes frequencies.A statistically significant association of the rare T allele of rs11591147 with low total cholesterol was determined.

familial hypercholesterolemia, proprotein convertase subtilisin/kexin 9 gene, population

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