Genetics, Epigenetics and GenomicsP51Novel T(-4661)C polymorphic allele variant of ABCA1 gene

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Abstract

ATP-binding cassette transporter A1 (ABCA1) is a main participant in reverse cholesterol transport (RTC) and can be implicated in atherosclerosis development. Liver X receptors (LXR) directly promote cholesterol efflux from macrophages, the first critical step of RTC, up-regulating ABCA1. There are sites for nuclear liver X receptors (LXR) in promote and 5′ flanking regions of ABCA1 gene. We suggest that polymorphic alleles in this region cay be associated with modulated level expression of ABCA1 gene. Purpose of our study was to search polymorphic alleles in 5′ flanking regions of ABCA1 gene and investigate their role in atherosclerosis development. Single-nucleotide polymorphism (SNP), which was not described previously, T(-4661)C of ABCA1 gene (NCBI, Gene Bank, AF275948) was found using SSCP analysis and direct sequencing of 5′ flanking region of ABCA1 gene among patients with extensive atherosclerosis and plasma HDL-C level lower than 0.9 mmol/l. For identification of T(-4661)C SNP a method, including PCR and restriction fragment length polymorphism analysis using endonuclease TaaI, was developed. We have showed that T(-4661)C SNP is widely spread in Russians. Genotypes TT(-4661), CT(-4661) и CC(-4661)frequencies were 81,32%, 17,58%, 0,00% и 78,35%, 21,64%, 0,75% among patients with angiographically verified atherosclerosis and control group, respectively. There were no differences in allele frequencies distribution of T(-4661)C SNP of ABCA1 gene between patients and control group. We can conclude that probably variants T(-4661)C of ABCA1 gene do not affect the atherosclerosis development. However further research is necessary to learn about influence of T(-4661)C variant on ABCA1 gene expression.

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