Influence of dihydrofolate reductase gene polymorphisms rs408626 (-317A>G) and rs442767 (-680C>A) on the outcome of methotrexate-based maintenance therapy in South Indian patients with acute lymphoblastic leukemia

European Journal of Clinical Pharmacology
Sunitha KodidelaDebdatta Basu

Abstract

The most common cause of treatment failure in acute lymphoblastic leukaemia (ALL) is the relapse. Genetic polymorphisms of dihydrofolate reductase (DHFR) enzyme affect the response to methotrexate (MTX) treatment. Inter-individual variability exists in the distribution of DHFR variants, and they influence MTX treatment outcome. To the best of our knowledge, there are no genetic studies reported from India, which have explored the influence of DHFR variants on the outcome of MTX treatment. Therefore, we aim to study the influence of DHFR rs408626 (-317A>G) and rs442767 (-680C>A) variants on ALL outcome in South Indian patients. A total of 70 ALL patients who were on MTX-based maintenance therapy were recruited for the study. DNA was extracted from leukocytes, and genotyping was done by real-time PCR. The DHFR-317GG genotype was associated with the increased risk of relapse in patients with ALL (relative risk 2.25, 95% confidence interval (CI) 1.38 to 3.6, p = 0.02). DHFR-317AA and -680CA genotypes were found to be associated with severe leucopenia (p < 0.05). In Cox regression model, -317GG genotype was found to have lower relapse-free survival (hazard ratio (HR) 2.56, 95% CI 1.06 to 6.19, p = 0.03) and overall survival (HR 3.72...Continue Reading

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Sep 13, 2016·International Journal of Molecular Sciences·Vid MlakarMarc Ansari
Apr 6, 2019·Expert Opinion on Drug Metabolism & Toxicology·Yuqing GongSantosh Kumar
Feb 2, 2019·Current Drug Metabolism·Guillermo Gervasini, Sonia Mota-Zamorano
Dec 25, 2019·Pediatric Hematology and Oncology·Rizal Husaini RazaliMohd Zaki Salleh
Aug 28, 2020·Pharmacogenomics and Personalized Medicine·Dimitri MaamariNathalie K Zgheib

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