We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Pharmacogenetic Variants in MTHFR Gene are Significant Predictors of Methotrexate Toxicities in Bangladeshi Patients With Acute Lymphoblastic Leukemia.
- Authors
Zahra, Fatema Tuz; Nahid, Noor Ahmed; Islam, Md. Reazul; Al-Mamun, Mir Md. Abdullah; Apu, Mohd Nazmul Hasan; Nahar, Zabun; Kabir, Amin Lutful; Biswas, Subrata K.; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Hasnat, Abul
- Abstract
<bold>Background: </bold>The objective of this pharmacogenetic study was to investigate the relationship of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms with methotrexate (MTX)-induced toxicities and plasma homocysteine level in patients with acute lymphoblastic leukemia (ALL) from Bangladesh. Several polymorphisms result in reduced MTHFR activity that causes impaired remethylation of homocysteine to methionine and abnormal MTX metabolism, especially in tissues with high turnover. Therefore, the risk of elevated plasma homocysteine as well as MTX-induced toxicities become higher with MTHFR polymorphisms.<bold>Patients and Methods: </bold>We recruited 160 patients with ALL receiving MTX containing chemotherapeutic protocol, and they were genotyped for MTHFR C677T and A1298C polymorphisms with polymerase chain reaction-restriction fragment length polymorphism. We also measured the plasma homocysteine level of 51 patients by the AxSYM homocysteine assay method.<bold>Results: </bold>We found 68.1% CC, 26.3% CT, and 5.6% TT genotype for MTHFR C677T polymorphism and 39.3% AA, 46.9% AC, and 13.8% CC genotype for MTHFR A1298C polymorphism in patients with ALL. Our study suggested that MTX-induced mucositis and diarrhea are significantly associated with MTHFR C677T as well as MTHFR A1298C polymorphisms (P < .05).<bold>Conclusion: </bold>The risk of elevated plasma homocysteine level was 5 to 6 times higher for both polymorphisms. This study may help to identify the patients who are at higher risk for MTX-related toxicities.
- Subjects
BANGLADESH; LYMPHOBLASTIC leukemia; METHOTREXATE; OXIDOREDUCTASES
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2020, Vol 20, Issue 2, pe58
- ISSN
2152-2650
- Publication type
journal article
- DOI
10.1016/j.clml.2019.11.020