Association Between MTHFR Genetic Variants and Multiple Sclerosis in a Southern Iranian Population

Area of Science:

• Neuroimmunology
• Genetics
• Autoimmune Diseases

Background:

• Multiple sclerosis (MS) is a central nervous system autoimmune disease.
• Genetic factors are implicated in MS etiology.
• The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in MS risk requires further investigation across diverse populations.

Purpose of the Study:

• To investigate the association between MTHFR gene variants (C677T and A1298C) and the risk of developing MS.
• To analyze the combined effects of these MTHFR polymorphisms on MS susceptibility.
• To evaluate these genetic associations within a Southern Iranian population.

Main Methods:

• Genotyping of MTHFR C677T and A1298C variants using mutagenically separated PCR (MS-PCR) and PCR-RFLP.
• Case-control study design with 180 MS patients and 231 healthy controls.
• Statistical analysis including odds ratio (OR) and 95% confidence intervals (95% CI) for risk assessment.

Main Results:

• Significant association observed between MTHFR C677T variants (CT and TT genotypes) and increased MS risk (ORs ranging from 2.9 to 6.23).
• The MTHFR A1298C variant (AC genotype) also showed increased MS risk (OR=2.14).
• Combined analysis revealed substantially elevated MS risk with specific genotypes (e.g., TT/AC, OR=13.9), suggesting a gene dose-dependent effect.

Conclusions:

• MTHFR gene polymorphisms (C677T and A1298C) are associated with an increased risk of multiple sclerosis in the studied population.
• A potential gene dose-dependent relationship exists between MTHFR mutant alleles and MS susceptibility.
• These findings contribute to understanding the genetic underpinnings of MS in different ethnic groups.