Protein C Promotor Haplotypes Associated with Large-Artery Atherosclerosis Stroke in Iranian Population

• Published in: Journal of molecular neuroscience 2021-10, Vol.71 (10), p.2134-2141
• Main Authors: Meshkani, Seyed Elyas, Fasihi, Ali, Badakhshan, Fatemeh, Zahedi, Mohmmadsaeid, Goudarzian, Maryam, Ramazi, Shahin
• Format: Article
• Language: English
• Subjects: Aged; Arteriosclerosis; Atherosclerosis; Atherosclerosis - complications; Atherosclerosis - genetics; Atherosclerosis - pathology; Binding; Biochemical analysis; Biomedical and Life Sciences; Biomedicine; Blood coagulation; Cell Biology; Cholesterol; Deoxyribonucleic acid; DNA; Female; Genetic diversity; Genetics; Genotyping; Haplotypes; Health risks; Humans; Hypertension; Iran; Ischemia; Ischemic Stroke - etiology; Ischemic Stroke - genetics; Ischemic Stroke - pathology; Male; Microprocessors; Middle Aged; Neurochemistry; Neurology; Neurosciences; Nucleotides; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Protein C; Protein C - genetics; Proteins; Proteomics; Risk analysis; Risk factors; Single-nucleotide polymorphism; Stroke; Thromboembolism; Thrombosis; Transcription factors
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-021-01819-5

Ischemic stroke (IS) is a complex disease regarding its risk factors; among those factors, genetics has an important role. Protein C (PC) is an important antithrombotic enzyme which its genetic variations disrupt the normal cascade of blood coagulation, resulting in thrombosis and increases the chance of stroke. Therefore, we aimed to investigate three single-nucleotide polymorphisms (SNPs) located in the core promoter of PC in order to find their role in this condition in the Iranian population. Blood samples from IS patients ( n  = 249) and healthy volunteers ( n  = 203) were collected. Biochemical analysis was performed. Genotyping was conducted on the extracted DNA from blood samples via the HRM technique. Bioinformatic investigations were used to assess how these SNPs may be involved in the IS. Smoking, hypertension, low-density lipoprotein cholesterol, and fasting blood glucose were significantly different between healthy and IS groups. rs1799809 and rs1799810 SNPs were significantly more frequent among IS patients. Also, among four identified haplotypes, CGT was found associated with IS ( p  = 0.001). It was also found that these SNPs may interfere with the binding of transcription factors to alter the expression of PC. Our data predict that SNPs at the core promoter of PC can affect the binding affinity of transcription factors which in turn reduces the expression of PC and increases the risk of IS.