S1PR1 gene polymorphism and IL-17 levels in Iranian Multiple Sclerosis patients treated with Fingolimod

Introduction:Multiple sclerosis (MS) is an inflammatory demyelinating andneurodegenerative disease of the central nervous system (CNS) with a multifactorialaetiology involving genetic factors. Fingolimod (Gilenya ®, FTY720)is a structural analogue of sphingosine, modulates the G-protein-coupledsphingosine 1-phosphate (S1P) receptors S1P1,2,3,4,5. Fingolimod is an orallyadministered in relapsing-remitting multiple sclerosis (RRMS). The S1PR1gene located on chromosome 1 (1p21). Studies showed the variation of thehuman S1P1 coding sequence results in heterogeneity in the function of thereceptor and impacts on the interaction of S1PR1 with fingolimod. Interleukin17 inhibits inflammatory processes.Materials and methods: Genomic DNA of 94 MS patients treated withfingolimod was extracted and The S1PR1 gene was determined by polymerasechain reaction (PCR). Direct Sanger Sequencing was performed to detect thepolymorphism of S1PR1 gene and flanking region on PCR products. Detectionof IL-17 from serum of patients, was performed by enzyme-linkedimmunosorbent assay (ELISA).Results: Among 94 relapsing-remitting MS patients treated with fingolimod69 (73.4%) of patients were responder and 25 (26.6%) of them were nonresponderto fingolimod. The results obtained from Sanger sequencingdetermined four novel SNPs and five common SNPs in MS patients.Discussion: The results suggest that response to treatment with fingolimodmaybe is not associated to the effect of S1PR1gene polymorphism. There wasno significant difference between IL-17 concentration before and aftertreatment with fingolimod. This study is the first study in Iran investigate theassociation of S1PR1 polymorphisms with IL-17 serum levels of Iranian MSpatients.

کلیدواژه ها:

S1PR1gene ، MS ، Fingolimod ، IL-17