BackgroundIschemic 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 inSERF2gene encoding the member of Hero-proteins, is associated with the risk of IS.MethodsA 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.ResultsAnalysis of the link between rs4644832SERF2and 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 rs4644832SERF2and 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).DiscussionSex- and smoking interactions between rs4644832 polymorphism and IS may be related to the impact of tobacco components metabolism and sex hormones onSERF2expression.ConclusionThe 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.