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

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

Polymorphism of HLa-DR and HLA-DQ in rheumatoid arthritis patients and clinical response to methotrexate - a hospital-based study

To investigate the frequency and distribution of DRB1 and DQB1 alleles in Patients with rheumatoid arthritis [RA] and analyze the relationship between clinical response to methotrexate [MTX] and the HLA-DR and HLA-DQ genotypes in these patients. In this case-control study, the HLA-DRB1 and HLA-DQB1 polymorphism in 91 RA patients and 91 healthy controls was done using polymerase chain reaction and sequence specific primers. There was no statistical difference in frequencies of HLA-DRB1*03, DRB1*04, DRB1*07, DRB1*10, DRB1*11, DRB1*12, DRB1*13, DRB1*14, DRB1*15 and DRB1*16 genotypes between patients and controls. However, DRB1*01 was found to be significantly more common [p=0.015] in RA patients compared to controls. HLA-DRB1*15 was more common in patients [43.5%] compared to controls [30.8%] but results were not significant. HLA-DRB1*08 and DRB1*09 were present in negligible number in patients as well as controls while HLA-DRB1*12 was conspicuously absent in controls. Similarly, DQB1*06 was also significantly more common [p = 0.01] among the patients compared to healthy control subjects, while there was no statistical difference in the frequencies of DQB1*02, DQB1*03, DQB1*04 and DQB1*05 among the cases and the controls. RA susceptibility in most patients appeared to be associated with the HLA-DRB1*01/DQB1*06 genotype. Regarding association between HLA-DR or HLA-DQ genotype and clinical response to methotrexate [MTX], the data showed that with the exception of HLA-DRB1*03, there appears to be no association between the particular subtypes of HLA-DR and HLA-DQ. HLA-DRB1*03 was significantly more common among non-responders to MTX alluding to the possibility that another genes responsible for MTX metabolism, might be in linkage disequilibrium with HLA-DRB1*03 in the Pakistani population, thereby making such individuals non-responsive to MTX-therapy. RA susceptibility in most Pakistani patients is associated with the HLA-DRB1*01/DQB1*06 genotype. HLA-DRB1*03 was found to be significantly more common among non-responders to MTX treatment suggesting that Pakistani patients with this genotype are less likely to benefit from MTX