SERPINE1 mRNA Binding Protein 1 Is Associated with Ischemic Stroke Risk: A Comprehensive Molecular–Genetic and Bioinformatics Analysis of SERBP1 SNPs

Author:

Shilenok Irina12,Kobzeva Ksenia1ORCID,Stetskaya Tatiana3,Freidin Maxim45,Soldatova Maria1,Deykin Alexey67ORCID,Soldatov Vladislav67,Churnosov Mikhail8ORCID,Polonikov Alexey39ORCID,Bushueva Olga19

Affiliation:

1. Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia

2. Division of Neurology, Kursk Emergency Hospital, 305035 Kursk, Russia

3. Laboratory of Statistical Genetics and Bioinformatics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, 305041 Kursk, Russia

4. Department of Biology, School of Biological and Behavioural Sciences, Queen Mary University of London, London E1 4NS, UK

5. Laboratory of Population Genetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Science, 634050 Tomsk, Russia

6. Laboratory of Genome Editing for Biomedicine and Animal Health, Belgorod State National Research University, 308015 Belgorod, Russia

7. Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, 308015 Belgorod, Russia

8. Department of Medical Biological Disciplines, Belgorod State University, 308015 Belgorod, Russia

9. Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 305041 Kursk, Russia

Abstract

The SERBP1 gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of SERBP1 have recently been discovered. The present pilot study investigated whether SERBP1 SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS). DNA samples from 2060 unrelated Russian subjects (869 IS patients and 1191 healthy controls) were genotyped for 5 common SNPs—rs4655707, rs1058074, rs12561767, rs12566098, and rs6702742 SERBP1—using probe-based PCR. The association of SNP rs12566098 with an increased risk of IS (risk allele C; p = 0.001) was observed regardless of gender or physical activity level and was modified by smoking, fruit and vegetable intake, and body mass index. SNP rs1058074 (risk allele C) was associated with an increased risk of IS exclusively in women (p = 0.02), non-smokers (p = 0.003), patients with low physical activity (p = 0.04), patients with low fruit and vegetable consumption (p = 0.04), and BMI ≥25 (p = 0.007). SNPs rs1058074 (p = 0.04), rs12561767 (p = 0.01), rs12566098 (p = 0.02), rs6702742 (p = 0.036), and rs4655707 (p = 0.04) were associated with shortening of activated partial thromboplastin time. Thus, SERBP1 SNPs represent novel genetic markers of IS. Further studies are required to confirm the relationship between SERBP1 polymorphism and IS risk.

Funder

Russian Science Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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