Association Between Multiple Sclerosis Severity and Functional Variants in Key Antioxidant Defense and...

Area of Science:

• Neuroimmunology
• Genetics
• Molecular Biology

Background:

• Multiple sclerosis (MS) is a chronic, inflammatory neurodegenerative disease.
• Oxidative stress and ferroptosis are key contributors to MS pathology, driving inflammation and neurodegeneration.
• Investigating genetic variations in antioxidant and ferroptosis pathways may reveal associations with MS progression.

Purpose of the Study:

• To explore the association between specific gene variants involved in antioxidant defense and ferroptosis and the progressive form of multiple sclerosis (MS).
• To analyze the impact of these variants on gene expression and molecular indicators of oxidative stress and ferroptosis in MS patients.

Main Methods:

• Genotyping of selected variants (GCLC rs572496, GCLM rs2273406, GPX4 rs713041, NQO1 rs1800566, CAT rs2420388) in 845 MS patients using TaqMan® technology.
• Quantification of mRNA expression levels for corresponding genes in peripheral blood mononuclear cells (PBMCs).
• Measurement of circulatory molecular indicators of antioxidant defense and ferroptosis via ELISA and enzymatic assays.

Main Results:

• The GCLC rs572496 variant showed a significant association with MS disease severity and influenced GCLC mRNA levels.
• The NQO1 rs1800566 variant significantly affected NQO1 mRNA expression in the PBMCs of all MS patients studied.
• These findings highlight potential roles for specific genetic variants in MS pathogenesis.

Conclusions:

• The study identifies specific genetic variants (GCLC rs572496, NQO1 rs1800566) associated with MS severity and gene expression.
• Further research with larger cohorts is recommended to validate these findings and explore the therapeutic potential of targeting antioxidant and ferroptosis pathways in MS.