Author/Authors :
Torbati، Sara نويسنده Department of Neurogenetics, Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran , , Karami، Fatemeh نويسنده , , Ghaffarpour، Majid نويسنده Professor of Neurology, Iranian Center of Neurological Research , , Zamani، Mahdi نويسنده Department of Neurogenetics, Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran ,
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-B) 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-B 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-B 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-B t herapy.
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.
