The link between proprotein convertase subtilisin/kexin 9 serum levels and E670G gene polymorphism and the risk of ischemic stroke in patients of the south of Egypt

Ezzat, Ghada M.; Nasreldein, Ahmed; Mohamed, Ghada A.; Elsewify, Wael Abdelgwad; Dahpy, Marwa A.

doi:10.4103/JCMRP.JCMRP_47_20

The link between proprotein convertase subtilisin/kexin 9 serum levels and E670G gene polymorphism and the risk of ischemic stroke in patients of the south of Egypt

Authors

Abstract

Background
Proprotein convertase subtilisin/kexin 9 (PCSK9) has a role in low-density lipoprotein-cholesterol metabolism, which relates to the initiation and progression of atherosclerosis and hence cerebrovascular ischemic stroke (CIS). This hospital-based study aims to investigate whether PCSK9 serum levels and single nucleotide polymorphism (SNP) of the PCSK9 gene associated with a higher incidence of atherosclerosis and CIS among a patient series in the south of Egypt or not.
Materials and methods
A total of 100 patients with ischemic stroke (68 with atherosclerotic ischemic stroke and 32 nonatherosclerotic ischemic stroke), together with 100 age-matched and sex-matched healthy controls, were enrolled in this study. Genotyping of SNP was performed by restriction fragment length polymorphism PCR. The serum PCSK9 levels were determined using ELISA kit, whereas serum lipid profiles were determined using colorimetric methods.
Results
Higher serum PCSK9 levels were significantly noticed in atherosclerotic ischemic stroke. Genotyping distribution of gene polymorphism of gene showed higher distribution in both patients with ischemic stroke and those with atherosclerotic ischemic stroke. The GA heterozygous carriers were at risk of developing ischemic stroke (odds ratio = 2.234, confidence interval = 1.2323–4.0509, = 0.0081) when compared with controls. Carriers of G allele of SNP had significantly higher serum total cholesterol and low-density lipoprotein-cholesterol levels in atherosclerotic ischemic stroke subgroup.
Conclusion
Serum PCSK9 levels were significantly higher among patients with atherosclerotic CIS. The gain-of-function mutation in carriers of the G allele of SNP plays an essential role in the pathogenesis of lipid related diseases, and it affects atherogenesis. These findings make the G allele of SNP of gene a possible genetic risk factor for ischemic stroke among atherosclerotic patients.

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