S1PR1 genetic variants may modulate disability outcomes and therapy response in relapsing-remitting multiple sclerosis

Sphingosine-1-phosphate receptor 1 (S1PR1) modulators are an effective therapy for patients with relapsing-remitting multiple sclerosis (RRMS), although considerable inter-individual variability in treatment response remains. This study aimed to investigate genetic variability within the coding regions of S1PR1 and to assess its potential association with treatment response and clinical disability measures, including the Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS), in patients with RRMS. Thirty-one RRMS patients from Serbia underwent sequencing of the 5′ regulatory region and coding exons of S1PR1 using an Applied Biosystems 3130 Genetic Analyzer. Three polymorphic variants were identified. None of the analyzed variants demonstrated a significant association with treatment response. Despite the small sample size, rs41287280 showed a significant association with disability measures; in a dominant inheritance model, carriers of the G allele had lower EDSS and MSSS values (P=0.01 and P=0.006, respectively) compared with the CC genotype. In multivariable analyses, the rs41287280 G allele was associated with lower disability, whereas the rs3737577 T allele was associated with higher disability compared to the wild-type GG genotype after adjustment. These results provide preliminary evidence suggesting that S1PR1 genetic variation may be related to disease pathogenesis in RRMS, warranting further confirmation in larger, independent cohorts and, potentially, functional investigation.