Polymorphism of SERF2, the gene encoding a heat-resistant obscure (Hero) protein with chaperone activity, is a novel link in ischemic stroke

Andrei E Belykh; Vladislav O Soldatov; Tatiana A Stetskaya; Ksenia A Kobzeva; Maria O Soldatova; Alexey V Polonikov; Alexey V Deykin; Mikhail I Churnosov; Maxim B Freidin; Olga Y Bushueva

doi:10.1016/j.ibneur.2023.05.004

Polymorphism of SERF2, the gene encoding a heat-resistant obscure (Hero) protein with chaperone activity, is a novel link in ischemic stroke

IBRO Neurosci Rep. 2023 May 10:14:453-461. doi: 10.1016/j.ibneur.2023.05.004. eCollection 2023 Jun.

Authors

Affiliations

¹ Pathophysiology Department, Kursk State Medical University, Kursk, Russia.
² Laboratory of Genome Editing for Veterinary and Biomedicine, Belgorod State National Research University, Belgorod, Russia.
³ Laboratory of Statistical Genetics and Bioinformatics, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia.
⁴ Laboratory of Genomic Research, Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia.
⁵ Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia.
⁶ Department of Medical Biological Disciplines, Belgorod State National Research University, Belgorod, Russia.
⁷ Laboratory of Population Genetics, Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Science, Tomsk, Russia.
⁸ Queen Mary University of London, London, United Kingdom.

Abstract

Background: Ischemic stroke (IS) is one of the most serious cardiovascular events associated with high risk of death or disability. The growing body of evidence highlights molecular chaperones as especially important players in the pathogenesis of the disease. Since six small proteins called "Hero" have been recently identified as a novel class of chaperones we aimed to evaluate whether SNP rs4644832 in SERF2 gene encoding the member of Hero-proteins, is associated with the risk of IS.

Methods: A total of 1929 unrelated Russians (861 patients with IS and 1068 healthy individuals) from Central Russia were recruited into the study. Genotyping was done using a probe-based PCR approach. Statistical analysis was carried out in the whole group and stratified by age, gender and smoking status.

Results: Analysis of the link between rs4644832 SERF2 and IS showed that G allele is the risk factor of IS only in females (OR=1.29, 95%CI 1.02-1.64, Padj=0.035). In addition, the analysis of associations of rs4644832 SERF2 and IS depending on the smoking status revealed that this genetic variant is associated with an increased risk of IS exclusively in non-smoking individuals (OR=1.26, 95%CI 1.01-1.56, P = 0.041).

Discussion: Sex- and smoking interactions between rs4644832 polymorphism and IS may be related to the impact of tobacco components metabolism and sex hormones on SERF2 expression.

Conclusion: The present study reveals the novel genetic association between rs4644832 polymorphism and the risk of IS suggesting that SERF2, the part of the protein quality control system, contributes to the pathogenesis of the disease.

Keywords: Chaperones; Heat-resistant obscure; Hero; Ischemic stroke; Rs4644832; SERF2.