title: Short Communication: 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 µmol/l vs. 11.4 ± 5.3 µmol/l; p<0.001). MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients.
authors.affiliation: Departments of Biological & Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan.
authors.forename: Mohammad Perwaiz
authors.initials: MP
authors.lastname: Iqbal
authors.affiliation: Departments of Medicine, Aga Khan University, Stadium Road, Karachi, Pakistan.
authors.forename: Azra Arif
authors.initials: AA
authors.lastname: Ali
authors.affiliation: Departments of Biological & Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan.
authors.forename: Naseema
authors.initials: N
authors.lastname: Mehboobali
authors.affiliation: Departments of Biological & Biomedical Sciences, Aga Khan University, Stadium Road, Karachi, Pakistan.
authors.forename: Khalida
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate