VDR gene polymorphisms predict treatment response in Latvian multiple sclerosis cohort

Background Vitamin D receptor (VDR) polymorphisms can modulate immune pathways and may influence the efficacy of disease-modifying therapies (DMTs) in multiple sclerosis (MS).
Aim To determine whether four common VDR single-nucleotide polymorphisms (SNPs) affect two-year therapeutic outcomes in Latvian MS patients.
Methods We genotyped rs2228570, rs1544410, rs7975232 and rs731236 by RFLP in 230 patients (342 DMT courses). Clinical response was defined as a change in the Expanded Disability Status Scale (EDSS) and the maintenance of “no evidence of disease activity” (NEDA) within two years after therapy initiation.
Results and Discussion
Homozygous CC (rs2228570) and TT (rs731236) and heterozygous GA (rs1544410) genotypes were linked to greater EDSS worsening under glatiramer acetate (p < 0.05). The GA genotype of rs1544410 also predicted a higher EDSS in year 2 among interferon-treated patients (p < 0.05). No significant genotype effect was observed for rs7975232.
These data indicate genotype-dependent variability in DMT response, suggesting that VDR polymorphisms modulate the clinical efficacy of glatiramer acetate and interferon in MS.
Conclusions Variants rs2228570, rs731236 and rs1544410 of the VDR gene may serve as pharmacogenetic markers to guide personalised DMT selection in Latvian MS patients.
Funding UL project 1.1.1.2/VIAA/4/20/718; ERDF 1.1.1.1/16/A/016; UL Foundation (MikroTik) 40021. (228 words)