No Association between Single-Nucleotide Polymorphisms of The S1PR1 Gene or Interleukin-17 Levels with Fingolimod Response in A Small Group of Iranian Relapsing-Remitting Multiple Sclerosis Patients: A Case-Control Study

Objective

Multiple sclerosis (MS) has a multi-factorial etiology involving genetic factors. Fingolimod (Gilenya ®, FTY720) modulates the G-protein-coupled sphingosine 1-phosphate (S1P) receptors, S1PR1, 2, 3, 4 and 5. Variation in the human S1PR1 coding sequence results in heterogeneity in the function of the receptor. Interleukin-17, producing CD4+ T cells, tends to be increased after treatment with Fingolimod. The aim of the study was to investigate single-nucleotide polymorphisms (SNPs) in the S1PR1 gene or interleukin-17 (IL-17) levels in a small group of Iranian relapsing-remitting MS patients treated with Fingolimod.

In this case-control study, the genomic DNA of 94 MS patients treated with Fingolimod was extracted and Sanger sequencing was performed on polymerase chain reaction (PCR) products to detect variants in the S1PR1 gene. Quantification of IL-17 from the serum of the patients was performed using a commercially available enzyme-linked immunosorbent assay (ELISA).

Among 94 relapsing-remitting MS patients treated with Fingolimod, 69 (73.4%) were responders and 25 (26.6%) were non-responders. There were four novel and five common SNPs in the S1PR1 gene and no significant association between SNP genotype and drug response was detected. In a subset of 34 patients, there was no significant difference in IL-17 serum concentrations before or after treatment and no association with S1PR1 polymorphisms was determined.

This study is the first in Iran to investigate association between SNPs of the S1PR1 gene or IL-17 levels with fingolimod response in a small group of Iranian relapsing remitting MS patients. There was no association with S1PR1 gene SNPs or IL-17 levels before or after treatment.