Association of Genetic Polymorphisms of Molecules in JAK-STAT Signaling Pathway with Susceptibility of Multiple Sclerosis

Abstract

Background: Multiple sclerosis (MS) is a disease that is characterized by demyelination of the central nervous system. The pathogenesis is associated with heredity, the environment and autoimmunity. The JAK-STAT (Janus kinase-signal transducer and activator of transcription) signalling pathway is mediated by a variety of cytokines, and may be involved in cell proliferation, differentiation, apoptosis and immune regulation. We aimed to study the association of genetic polymorphisms of molecules in the JAK-STAT signalling pathway with the susceptibility to MS. Methods: We collected 110 patients with MS and 110 healthy volunteers as negative controls. Venous blood was extracted from all patients with MS and healthy volunteers. Genes related to JAK-STAT signalling pathways associated with MS susceptibility were screened through literature retrieval and gene clustering database. The gene polymorphisms were genotyped using modified ligase reaction (iMLDR) technology. SPSS 16.0 software was used to compare the differences between MS patients and healthy controls. Results: The genotype frequencies of 10 polymorphisms of STAT3 (signal transducer and activator of transcription 3) (rs4796791, rs744166 and rs2293152), STAT4 (rs9967792), IL7R (interleukin 7 receptor) (rs6897932 and rs6881706), IL2RA (interleukin 2 receptor A) (rs12722489 and rs2104286), and IL12A (interleukin 12A) (rs1014486 and rs4680534) in the JAK-STAT signalling pathway were not significantly different between the patients with MS and the healthy controls (p > 0.05). When stratified by sex, the female subjects who carried STAT3 (rs2293152) CG had an increased risk of MS when compared to those who carried the GG allele (odds ratio (OR) = 2.596, 95% confidence interval (CI): 1.131 5.959, p = 0.023);The male subjects who carried IL7R (rs6881706) GT had a decreased risk of MS when compared to those who carried the GG allele (OR = 0.175, 95% CI: 0.034 0.892, p = 0.023). Conclusions: Polymorphisms in the STAT3 (rs4796791 and rs744166), STAT4 (rs9967792), IL7R (rs6897932), IL2RA (rs12722489 and rs2104286), and IL12A (rs1014486 and rs4680534) genes in the JAK-STAT signalling pathway were not associated with MS susceptibility in northern China. Females with the STAT3 (rs2293152) CG genotype may have an increased susceptibility to MS, and male with the IL7R (rs6881706) GT genotype may have a reduced MS susceptibility.