The effects of Endothelial Protein C Receptor Gene Polymorphisms on sEPCR levels in Venous Thrombotic Patients

Abstract

OBJECTIVE: The aim of this study was to investigate the detection of the variations in the EPCR gene which has a possible role for thrombosis and the effects of this variations on the plasma sEPCR levels in Turkish population. METHODS: This study included 111 thrombotic patients and 73 healthy controls. Following DNA extraction, PCR, SSCP and DNA sequencing analysis of four exons of the EPCR gene were performed. Plasma sEPCR levels were measured with Enyzme linked immunosorbent assay (ELISA). RESULTS: Three polymorphisms were detected in exon 1 through exon 4. The C3998T (SNP no: rs2069952) is located within intron 2 and the C4678G (A1 haplotype) (SNP no: rs9574) is located within 3' untranslated region (3'UTR). There was no significant differences between C3998T polymorphism in control and patients. There was no significant difference in sEPCR levels in subjects carrying A1 allele. A4600G substitution (A3 haplotype) (SNP no: rs867186) was found in exon 4 and it brought 2.04 fold risk for thrombosis. A3 allele carriers had high sEPCR levels, compared to no A3 allele carriers. The mean sEPCR level in patients having A3 allele homozygous is 289 ng /ul and A1 allele homozygous is 113,42 ng/ul. CONCLUSION: A1 haplotype might have a protective effect on thrombosis and A3 haplotype may be associated both with increased plasma sEPCR levels and with an increased risk of venous thrombosis in Turkish population. sEPCR levels were significantly higher in subjects carrying A3 allele (4600A>G) in both patients and controls. There was no significant difference in sEPCR levels in subjects carrying A1 allele (4678C>G).

Keywords

• thrombosis
• endothelial protein c receptor (epcr)
• soluble epcr (sepcr)
• epcr haplotypes.