The Prevalence of SNP rs12517451 in Gene Transcribing Dihydrofolate Reductase and Drug Adverse Effects among MTX-treated Rheumatoid Arthritis Patients in Kelantan, Malaysia

ABSTRACT

@#Introduction: Disease-modifying anti rheumatic drugs (DMARDs) provide the mainstay for the treatment of rheumatoid arthritis (RA). Adverse effects (AEs) in DMARDs among RA patients are usually related with methotrexate (MTX) use, the common conventional DMARDs. Genetic variant such as single nucleotide polymorphism (SNP) in gene transcribing dihydrofolate reductase (DHFR) (i.e, 829C>T, rs12517451) has been correlated with drug AEs in MTX-treated RA. The prevalence of the DHFR rs12517451 SNP has been reported in other populations, but not in Malaysian. The aim of this study was to determine the prevalence of the DHFR rs12517451 SNP and its association with drug AEs among MTX-treated RA patients from Kelantan, Malaysia. Methods: A total of 78 RA patients receiving MTX (alone or in combination) were included in this study. Based on evidence of clinically perceived drug AEs in MTX-treated RA patients, 33 and 45 samples were assigned as cases and controls, respectively. The genotype of the patients was determined using the polymerase chain reaction-restriction fragment length polymorphism method and validated by sequencing analysis. Results: Minor allele frequency (MAF) for DHFR rs12517451 in cases and controls were 28.8% and 32.2% but there was no significant difference (p=0.727) for the possession of the minor allele T between the two groups. The most reported AEs among cases were haematological effects, gastrointestinal toxicity, and skin problems resulting in 21% withdrawal of MTX. Conclusion: We did not find significant association of the DHFR rs12517451 with drug AEs in MTX-treated RA patients. Our findings warrant replication in a larger patient cohort.