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

Document Type : Original Article

Authors

1 Cancer Molecular Pathology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran

2 Neurological Ward, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

3 Section of Molecular Biology, Institute of Medical and Biomedical Education, St George’s University of London, Cranmer Terrace, SW17 0RE, London, UK

10.22074/cellj.2024.2012548.1415

Abstract

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.
Materials and Methods: 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).
Results: 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.
Conclusion: 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.

Keywords

Main Subjects

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