الفهرس 
RHEUMATOID ARTHRITISOnly 14 pages are availabe for public view
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Abstract
T
he prognosis for RA has been improved by the development of novel treatments, particularly DMARDs. MTX is one of the most widely used DMARDs in clinical practice, due to its proven efficacy and low cost. However, 40–60% of RA patients do not achieve a satisfactory response to DMARDs and about 15–30% develop adverse effects. Thus, the outcome of MTX treatment varies unpredictably between RA patients.
Methotrexate is an antifolate drug that displays antiproliferative and anti-inflammatory effects by inhibiting several key enzymes involved in folate, methionine, adenosine, and de novo nucleotide synthesis pathways.
Methylene tetrahydrofolate reductase is a central regulatory enzyme in the folic acid pathway, which is required for the regeneration of reduced folate, and is indirectly inhibited by MTX. This enzyme is a regulated by the MTHFR gene. The alteration of enzyme activity as a result of the gene mutation remains controversial.
On the light of the previous data, the present study was conducted to investigate the impact of MTHFR gene C677T (rs1801133) polymorphism on the clinical outcome of MTX treatment as regards treatment efficacy or toxicity in Egyptian rheumatoid arthritis patients.
Subjects in this study were recruited from the in-patient ward and the outpatient clinic of the Internal medicine Rheumatology and Immunology Department and conducted at the Clinical Chemistry Laboratory, Clinical Pathology Department, Ain Shams University Hospitals. The included subjects were classified into 45 patients diagnosed with RA receiving MTX as a first line of treatment 25 in group I (Responders Group) and 20 in group II (Non-Responders Group). Detection of the MTHFR gene polymorphism by real-time PCR was done for both the responders and the non-responders groups.
The present study did not confirm the presence of significant association between the genotypic frequencies of the MTHFR gene C677T (rs1801133) polymorphism among the responders and the non-responders group in patients with RA. The MTHFR gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders group in patients with RA.
Our findings suggest that statistically significant difference was found between the responders to the treatment and non-responders in disease activity (DAS 28) in patients with RA. There were statistically significant higher rates of hematologic toxicity in the CC group of the responders and in the TT group in the non-responders. Regarding renal toxicity in all patients groups, C allele showed statistically significant these groups.
In conclusion, the current study revealed that no significant association between the genotypic frequencies of the MTHFR gene C677T (rs1801133) polymorphism among the responders and the non-responders group in patients with RA. Moreover, the MTHFR gene C677T (rs1801133) polymorphism did not show significant difference between disease complications among the responders and the non-responders group in patients with RA.
RECOMMENDATIONS
Further studies with larger sample size are recommended to clarify the statistical significance of the association of the genotypic frequencies of the MTHFR gene C677T (rs1801133) polymorphism in patients with RA.
Future studies that report the effect of the MTHFR gene C677T (rs1801133) polymorphism on disease complications among RA patients.
Presence of large-scale genetic studies based on the haplotyping of different SNPs in order to be more influential than the study of a single SNP.