A duplex polymerase chain reaction‐restriction fragment length polymorphism for rapid screening of methylenetetrahydrofolate reductase gene variants: Genotyping in acute leukemia

Rebaï

Mahmoud

et al. 2018

J Oncol Pharm Pract

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Context: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, mainly the C677T, have been implicated as risk factors for several cancers as the acute lymphoblastic leukemia (ALL). In addition, a potential effect of such variant on the efficacy of methotrexate (MTX) has been reported. Objective: In this study, we evaluated the impact of the C677T variant of MTHFR on MTX-related toxicity in ALL patients from Tunisia; to provide new insights for a personalized therapy based on the human genotype. Materials and methods: Genotyping was carried out with restriction fragment length polymorphism (RFLP) on blood samples from a total of 35 younger patients; suffering from ALL. Results: In the ALL patients, the MTHFR 677CT genotype confers a greater risk of toxicity with 1.3 times as relative risk mainly the hepatic toxicity when compared with MTHFR 677CC. Conclusion: Our findings suggest that C677T polymorphism of MTHFR seems to be a good marker for MTX-related toxicity in ALL.

Section: Laboratory Methodsmentioning

confidence: 99%

Comprehensive analysis of Methylenetetrahydrofolate reductase C677T in younger acute lymphoblastic leukemia patients: A single-center experience

Rebaï

Mahmoud

et al. 2018

J Oncol Pharm Pract

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“…After DNA extraction, the polymerase chain reaction using specific primers was conducted as previously described. 6…”

Section: Methodsmentioning

confidence: 99%

Involvement of C677T MTHFR variant but not A1298C in methotrexate-induced toxicity in acute lymphoblastic leukemia

Jemaa

et al. 2020

J Oncol Pharm Pract

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Background Methotrexate (MTX) is a key drug in acute lymphoblastic leukemia (ALL) treatment; it inhibits DNA replication by blocking the conversion of 5, 10 Methylenetetrahydrofolate to 5-methylene tetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). Variants of the Methylenetetrahydrofolate reductase (MTHFR) and MTX related toxicities were largely investigated in several populations, nevertheless, the results are conflicting. Objective This study aimed to assess the prevalence of MTHFR SNVs: C677>T and A1298>C in Tunisian patients with ALL and the relation to the frequency of drug-induced complications. Methods 28 ALL patients were included in the study. They were treated according to EORTOC, in which a high dose of MTX (HDMTX) was prescribed. A toxicity score (ST) is calculated for each patient, summing the grades of toxicities. Genotyping of MTHFR variants was done with a PCR-based restriction fragment length polymorphism assay. Results The toxicity’s score (TS) was higher with C677T variant compared to wild genotype (C677C) (TS = 4; IC95% [−2.65–13.32] versus TS = 2.5; IC95% [1.65–4.55], respectively; p = 0.2); but lower with the A1298C mutation compared to those with the wild genotype (A1298A) (TS = 2.5; IC95% [0.48–4.77], versus TS =3; IC95% [1.9–5.69], p = 0.4). HDMTX-related toxicity is associated with the 677CT genotype in ALL patients (RR = 1.41, p = 0.2); not for the A1298C [OR = 0.46, [0.08–2.61], p = 0.18]. Conclusion Our preliminary findings highlight the impact of the C677T variant of MTHFR, but not the A1289C; in HD-MTX chemotherapy-related adverse effects in younger Tunisian ALL.

“…Genotyping of MTHFR C677T was performed by a polymerase chain reaction-restriction fragment length polymorphism using specific primers and HinfI enzyme. 7 Allele frequencies of MTHFR rs1801133 and strengthens of association were analyzed by computing the odds ratios and 95% confidence interval. P < 0.05 was considered to indicate a statistically significant difference.…”

Section: Methodsmentioning

confidence: 99%

Involvement of MTHFR rs1801133 in the Susceptibility of Acute Lymphoblastic Leukemia: A Preliminary Study

Turki

Journal of Pediatric Hematology/Oncology

et al. 2020

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Background: Acute lymphoblastic leukemia (ALL), a common blood cancer, is characterized by the interaction between genetic and environmental factors. Several variants of the Methylenetetrahydrofolate reductase (MTHFR), mainly the C677T (rs1801133), may affect susceptibility to ALL. Aim of the Study: The authors conducted this case-control study to evaluate the relationship between this variant of the MTHFR gene and the risk of ALL. Materials and Methods: Forty-one patients with ALL and 35 non-ALL controls recruited in this study were genotyped utilizing polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The MTHFR 677CT genotype was significantly more frequently found in patients with ALL having a 2-fold increase in risk (P <0.01). Conclusion: Our results suggest that rs1801133 of MTHFR is a predictive risk marker to ALL in Tunisian ALL.