A population-based study of single nucleotide polymorphisms as risk factors for multiple sclerosis and neuromyelitis optica spectrum disorders (Yaroslavl region)

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) have a complex aetiology resulting from the interaction of genetic predisposition and environmental factors. Analysis of single nucleotide polymorphisms (SNPs) in genes associated with the immune response and neurodegenerative diseases plays a key role in elucidating the mechanisms underlying the development of these conditions, identifying population-level predispositions and discovering new targets for therapeutic intervention.

Objective: to determine the frequency of SNPs in genes involved in immune responses and neurodegenerative processes among patients with MS and NMOSD, using the Yaroslavl Region as a case study.

Material and methods. This cross-sectional, single-centre observational study included 10 patients with NMOSD (AQP4-IgG+), 63 patients with MS and 47 clinically healthy volunteers, who formed the control group. Genotypes for nine SNPs (IL6, IL6ST, CNTF, SOD2, SIRT1, TP53, PER2, MMP9) were determined using the FastPCR method. Statistical analysis of the data included descriptive statistics, as well as the c2 test and calculation of the odds ratio (OR) with a 95% confidence interval.

Results. Significant associations (p<0.05) were identified between carriage of certain alleles/genotypes and the presence of MS and/or NMOSD in the study population. The homozygous G/G genotype of the IL6 C174G polymorphism (rs1800795) was associated with an increased risk of disease (OR=4.00). An association was demonstrated between the minor allele A of the CNTF gene (rs1800169) and NMOSD. Carriage of the alternative allele T of the SOD2 C47T gene (rs4880) was less common in patient groups (OR=0.24). A strong association was identified between the minor allele G of the SIRT1 C(-1411)G gene (rs7069102) and the risk of both diseases (OR=16.45). Heterozygous A/G status of the PER2 A1984G (rs6343159) gene and the homozygous G/G genotype of the MMP9 A249G (rs17576) gene were also significantly more common in MS and NMOSD.

Conclusion. The findings confirm the significant role of polymorphisms in the IL6, SIRT1 and MMP9 genes as potential genetic markers of an increased risk of developing MS and NMOSD in the studied population. The findings regarding the associations between SNPs in the SOD2, CNTF and PER2 genes and these diseases are new for this population and require further investigation in a larger sample, particularly for the NMOSD group.

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