Polymorphisms in Base Excision Repair Genes and Association with Multiple Sclerosis in a Pilot Study on a Central...

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease involving demyelination and neurodegeneration.
• The etiology of MS is multifactorial, with genetic and environmental factors, including oxidative stress, playing potential roles.
• The base excision repair (BER) pathway is crucial for repairing oxidative DNA damage, a process implicated in MS pathogenesis.

Purpose of the Study:

• To investigate the association between polymorphisms in base excision repair (BER) genes and susceptibility to multiple sclerosis (MS).
• To analyze single nucleotide polymorphisms (SNPs) and haplotypes within BER genes in a Central European population.

Main Methods:

• Genotyping of ten SNPs across seven BER genes in 102 MS patients and 118 healthy controls.
• Statistical analysis including logistic regression for single SNP associations and haplotype analysis for SNPs in linkage disequilibrium.
• Multivariable logistic regression model used for SNPs not in linkage disequilibrium.

Main Results:

• Six SNPs showed significant associations with MS susceptibility.
• Increased MS risk was linked to specific SNPs in XRCC1, SMUG1, and MUTYH.
• Reduced MS risk was associated with SNPs in MBD4, MUTYH, and TDG, as well as a specific MUTYH haplotype (G-C).

Conclusions:

• Genetic variations in BER genes contribute to MS susceptibility.
• Both individual SNPs and haplotype combinations within BER genes impact MS risk.
• Further research is needed to elucidate the functional impact of these variants and validate findings in larger cohorts.