Lack of association between MTHFR gene polymorphisms and response to methotrexate treatment in Pakistani patients with rheumatoid arthritis

ABSTRACT

Methylenetetrahydrofolate reductase [MTHFR] gene polymorphisms have been reported to be associated with response to methotrexate [MTX] in certain populations of patients with rheumatoid arthritis [RA]. This study aims at investigating any relationship of two single nucleotide polymorphisms [SNPs] in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms [C677T and A1298C] were determined in 67 RA patients [9 males and 58 females; mean age 42.87 +/- 13.5 years] who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response up to 6 months. Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP, while fasting concentration of plasma homocysteine was determined using a kit method. Twenty-eight patients were found to be "good responders", while twenty-three were [poor responders]. MTHFR 1298C and MTHFR 677T alleles' frequencies in [good responders] were not different from frequencies in [poor responders] [0.574 vs. 0.521; p=0.6 and 0.197 vs. 0.196; p=0.75, respectively]. Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi [13.1 +/- 6.7 micromol/1 vs. 11.4 +/- 5.3 micromol/1; p<0.00l]. MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients