Association of 63/91 Length Polymorphism in the DHFR Gene Major Promoter with Toxicity of Methotrexate in Patients with c arthritis

Abstract

Aim: Our aim was to explore the influence of 9-bp insertion/deletion and variable number of 9 bp elements (63/91) length polymorphism in noncoding interfering RNA and major promoter of DHFR gene on methotrexate (MTX) efficacy and toxicity in patients with rheumatoid arthritis (RA). Patients & methods: Response to the MTX therapy and adverse effects were estimated in 243 RA patients genotyped for the selected polymorphism. Results: The presence of allele 1 of analyzed polymorphism had significant protective effect against MTX toxicity (odds ratio: 0.37 [95% CI: 0.19–0.70]; p = 0.002). Results remained significant in multiple logistic regression analysis with the inclusion of disease and treatment features in the model (p = 0.03). Conclusion: Polymorphism 63/91 in DHFR gene promoter can modulate the onset of MTX-related adverse effects in RA patients.

Keywords::

• dihydrofolate reductase
• interfering RNA
• methotrexate
• polymorphism
• rheumatoid arthritis

Financial & competing interests disclosure

This work was supported by Ministry of Education, Science and Technological Development of Republic of Serbia (grant no. 175091). The authors declare no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by Ministry of Education, Science and Technological Development of Republic of Serbia (grant no. 175091). The authors declare no conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.