Impact of HLA-DRB alleles on the role of IL-6 promoter polymorphism in an Iranian population with multiple sclerosis

Background: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) affecting most commonly the Caucasian population. The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. A single nucleotide polymorphism at position -174 in the IL- 6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles as a potential interpreter. Most of them have shown that HLA-DRB1*15 allele is a significant predisposing factor for developing MS. Objectives: The aim of this study was to investigate the possible influence of -174/-597 IL-6 polymorphisms on susceptibility toMS and its integrationwithHLA-DRB alleles. Methods: Genomic DNA was extracted from whole blood of 210 MS Patients and 264 age, ethnic and geographical matched control subjects. SSP-PCR method was used to determine genotyping and Fisher’s exact test was applied to determine differences between groups. Results: Frequency of G/G genotype was significantly higher in MS patients. In addition, combination of HLADRB alleles, DRB1*07, DRB1*16 and DRB1*14 with G/G genotype were found less frequent in MS patient than controls (p=0.0001, 0.02, 0.0001, respectively). Conclusions: Our results have shown that IL-6 -174 G/G genotype is strongly associated with development of multiple sclerosis in this population.Whereas, combination of G/G genotype with DRB1*07, DRB1*16 and DRB1*14 alleles positive, were more likely to protect against MS development. It seems that high production of IL-6 predicts susceptibility toMS; however, HLA-DRB alleles tone down IL-6 corollary in the Iranian population.