Polymorphisms in Genes Involved in Methotrexate Pathway: Predictor of Response to Methotrexate Therapy in Indian Rheumatoid Arthritis Patients

Ankita Singh¹, Harikrishnan Nair ², Vikas Gupta ², Pradeepta Sekhar ², Ramnath Misra ³ and Amita Aggarwal ⁴, ¹Sanjay Gandhi Post Graduate institute of medical science, Lucknow, India, Lucknow, Uttar Pradesh, India, ²Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, ³Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Lucknow, Uttar Pradesh, India, ⁴Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, Lucknow, Uttar Pradesh, India

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Biomarkers, methotrexate (MTX) and polymorphism, rheumatoid arthritis, treatment

Session Information

Date: Tuesday, November 12, 2019

Title: Genetics, Genomics & Proteomics Poster

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Methotrexate (MTX) is first line therapy to treat rheumatoid arthritis (RA) patients. However, the response is variable with 50-60% showing response and this variability could be related to single nucleotide polymorphisms (SNPs) in genes involved in MTX metabolism or action. Thus we studied association of eight polymorphisms [rs2236225 (MTHFD1 1958G >A), rs17602729 (AMPD1 G >A), rs1127354 (ITPA C >A), rs1431131 (TGFBR2 A >T), rs244076 (ADA T >C), rs2372536 (ATIC C >G), rs11188513 (ENTPD1 C >T), rs5751876 (ADORA2A T >C)] in the genes involved in MTX pathway with response to MTX therapy in Indian RA patients.

Methods: Genotyping of RA patients (EULAR/ACR 2010 criteria), DMARD naïve with active disease (DAS 28 >3.2) was done using by TaqMan 5′ nuclease assay. MTX monotherapy was given to the patients by gradually escalating the dose to a maximum of 25mg/week or maximal tolerated dose. Four months after therapy, based on EULAR response criteria patients were classified into responder and non-responder group. The association of SNPs with response to MTX therapy was assessed using Chi-Squared test.

Results: Two hundred seven patients (85.5% females; median-age 40 [17] years); median duration of disease 24 (40) months; median DAS28-CRP 4.82 (1.51) were enrolled. At 4 months, based on EULAR response 172 patients were classified as responders and 35 as non-responders. Assuming C dominance, recessive model of ITPA C >T [P = 0.004; OR (95% CI= 1.44 (1.05-1.97) associated with response to MTX. Assuming C dominance, dominant model [P = 0.019; OR (95% CI) = 4.07 (1.03-16.06)] and recessive model [P = 0.04; OR (95% CI) = 1.28 (0.96- 1.7)] of ATIC C >G associated with response to MTX. On multiple logistic regression analysis, ITPA C >T and DAS28-ESR at baseline were independent predictors of response to MTX.

Conclusion: Two polymorphisms i.e. ITPA C >T and ATIC C >G were associated with response to MTX therapy in Indian RA patients. Along with clinical variables only ITPA C >T had independent association with response to MTX.

Table 1-converted

Allelic and genotypic associations of polymorphism with response to Methotrexate.

Disclosure: A. Singh, None; H. Nair, None; V. Gupta, None; P. Sekhar, None; R. Misra, None; A. Aggarwal, None.

To cite this abstract in AMA style:

Singh A, Nair H, Gupta V, Sekhar P, Misra R, Aggarwal A. Polymorphisms in Genes Involved in Methotrexate Pathway: Predictor of Response to Methotrexate Therapy in Indian Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/polymorphisms-in-genes-involved-in-methotrexate-pathway-predictor-of-response-to-methotrexate-therapy-in-indian-rheumatoid-arthritis-patients/. Accessed .

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