MTHFR c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis

Area of Science:

• Genetics
• Immunology
• Pharmacology

Background:

• Rheumatoid arthritis (RA) is a prevalent autoimmune disease impacting 1% of the population.
• Current RA treatment focuses on achieving remission, but many patients inadequately respond to therapies.
• Tumor necrosis factor-α (TNF-α) inhibitors are used for treatment-resistant RA, yet response variability necessitates identifying predictive markers.

Purpose of the Study:

• To investigate the association between MTHFR gene polymorphisms (c.665C>T and c.1298A>C) and patient response to anti-TNF-α therapy in RA.
• To explore if these genetic variations can serve as response markers for anti-TNF-α treatment.
• To assess the potential influence of MTHFR polymorphisms on anti-TNF-α drug type efficacy.

Main Methods:

• Study included 81 RA patients undergoing anti-TNF-α therapy.
• Genotyping was performed for two MTHFR polymorphisms: c.665C>T and c.1298A>C.
• Statistical analyses were conducted to determine the association between genotypes and treatment response, including allele dose-dependency and drug type.

Main Results:

• Approximately 60% of patients responded to anti-TNF-α therapy.
• Both MTHFR polymorphisms showed an association with treatment response in an allele dose-dependent manner.
• The c.665C>T polymorphism was significantly associated with a rare genotype (p=0.01) and treatment response.
• The c.1298A>C polymorphism was significantly associated with the type of anti-TNF-α drug used (p=0.032).

Conclusions:

• MTHFR gene polymorphisms are associated with response to anti-TNF-α therapy in RA patients.
• The c.665C>T polymorphism may serve as a predictive marker for treatment response.
• The c.1298A>C polymorphism's association with drug type suggests a role in personalized RA interventions and highlights the involvement of one-carbon metabolism in anti-TNF-α efficacy.