Serum levels and genetic variation of IL-35 are associated with multiple sclerosis: a population-based case-control study

Abstract

This study aimed to investigate the association between serum levels and polymorphic variants of IL-35 with susceptibility, clinical features, and disease severity in multiple sclerosis (MS) patients.This case-control study recruited 186 MS patients and 195 sex- and age-matched healthy controls. Serum levels and polymorphic variants of IL-35 were determined by ELISA and restriction fragment length polymorphism (RFLP)-PCR or high resolution melting (HRM) analysis methods, respectively. In addition, by in silico analysis, we evaluated the location and function of the polymorphism.Serum levels of IL-35 were significantly lower in the patients than those of healthy controls (49.3 ± 3.7 vs. 69.5 ± 7.8, p = 0.009). EBI3 rs4740 polymorphism of IL-35 was associated with 2.2-fold increased risk of MS susceptibility (95% CI, 1.3-3.9, p = 0.005). However, there were no differences in the genotype distribution and allele frequencies of IL-35 rs568408 between the patients and controls (p > 0.05). In silico results showed that variation in IL-12A and EBI3 may affect on protein pathways of the cells and different components of the immune system such as NF-κB and INF-γ.The results show that IL-35 polymorphisms might be a genetic risk factor for the development of MS.

Keywords: EBI3; High resolution melt analysis; IL-35; Multiple sclerosis; Polymorphism.