Association of CD58 Polymorphism with Multiple Sclerosis and Response to Interferon ß Therapy in A Subset of Iranian Population

Abstract

Objective: Multiple sclerosis (MS) is one of the leading neurodegenerative causes of physical disability world-wide. Genetic aberrations of autoimmunity pathway components have been demonstrated to significantly influence MS development. Cluster of Differentiation 58 (CD58) is pertained to a group of genes which had been assayed in several recent association studies. Given the significance of CD58 in modulation of T regulatory cells that control autoimmune responses, the present study was conducted to investigate the frequency of rs12044852 polymorphism and its effect on the outcome of interferon beta (IFN-β) therapy in a subset of Iranian MS patients.

Materials and methods: Two hundred MS patients and equal number of healthy controls were recruited to be genotyped in an experimental case-control based study through polymerase chain reaction using specific sequence primers (PCR-SSP). Relapsing remitting multiple sclerosis (RRMS) patients administered IFN-β therapy were followed up with clinical visits every three months up to two years. The mean of multiple sclerosis severity score (MSSS) and expanded disability status scale (EDSS) were measured to monitor the change in severity of MS in response to IFN-β therapy. Pearson's Chi-square and analysis of variance (ANOVA) tests were the main statistical methods used in this study.

Results: Strong association was found between the CC genotype and onset of MS (p=0.001, OR=2.22). However, there was no association between rs12044852 and various classifications and severity of MS. Pharmacogenetics-based analysis indicated that carriers of CC genotype had the highest MSSS score compared to others, implying a negative impact of rs12044852 on response to IFN-β therapy.

Conclusion: Taken together, our findings revealed the critical effect of rs12044852 polymorphism of CD58 on the progression of MS disease. This indicates that genotyping of MS patients may expedite achieving personalized medical management of MS patients.

Keywords: CD58; Interferon β; Multiple Sclerosis; Polymorphism; Response.

Fig 1

The polymerase chain reaction by specific sequence primers (PCR-SSP) products separated on acrylamide gel (10%).

Fig 2

Association between response to IFN-β therapy and rs12044852 A/C polymorphism. MSSS (1); Multiple sclerosis severity score before treatment and MSSS (2); Multiple sclerosis severity score after treatment. ΔMSSS were 0.11, 0.03, 0.44 and 0.38 in MS patients with AA, AC, CC genotypes and total AD respectively. Total; All AD patients with any genotypes.