SLC19A1 hot spot for MTX plasma concentration

Gutiérrez-Camino, Ángela; López-López, Elixabet; Garcı́a-Orad, Africa

doi:10.1007/s12032-014-0204-4

Cited by 4 publications

(3 citation statements)

References 3 publications

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“…In fact, Treviño et al40 performed a genome-wide association study in patients with ALL and found rs4149081 and rs11045879 in SLCO1B1 strongly associated for the first time with MTX clearance, and this association was widely confirmed by subsequent studies 11,39,41. As a result, other works have focused their interest on the analysis of polymorphism in MTX transporters, finding several SNPs in genes such as SLC19A1 , ABCC4 , or ABCC2 also associated with MTX levels and other toxicities 42–44…”

Section: Resultsmentioning

confidence: 94%

MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

Umerez¹,

Gutiérrez-Camino²,

Muñoz-Maldonado³

et al. 2017

PGPM

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Methotrexate (MTX) is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes.

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Section: Resultsmentioning

confidence: 94%

MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

Umerez¹,

Gutiérrez-Camino²,

Muñoz-Maldonado³

et al. 2017

PGPM

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“…The studied polymorphism is the focused genetic background that is widely discussed for its effect on methotrexate dose in leukemia treatment. [4,7] In this study, it can be seen that the GG genotype requires the highest energy per mole which imply the least change in the formation of outcome. This is concordant with the report by Wang et al [4] Based our prediction, the amount of serum methotrexate in TT genotype is 1.10 and 1.20 times more than GT and GG, respectively.…”

Section: Discussionmentioning

confidence: 61%

SLC19A1 Polymorphism and Serum Methotrexate in Patients with Acute Lymphoblastic Leukemia

Joob

Wiwanitkit

2018

Indian Journal of Medical and Paediatric Oncology

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Acute lymphoblastic leukemia (ALL) is a common pediatric malignancy. Methotrexate is the widely used chemotherapy for ALL. The polymorphism (rs1051296) of SLC19A1 is proposed for its effect on serum methotrexate. To explain this observation, the authors hereby studied the interrelationship between SLC19A1 polymorphism and blood methotrexate level in the patients with ALL. Here, the authors use a quantum chemistry analysis for explaining of this observation.

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“…The strongest evidence is available for the R27H mutation. Several recent studies have associated the R27H mutation with increased MTX plasma concentration and toxicity, although no RFC-1 polymorphism has been found to significantly affect MTX response in GWAS analyses [41], [42], [43]. It is known that MTX responses differ between ethnic groups, especially between Asian and Caucasian populations [44].…”

Section: Pharmacogenetic Considerations For Mtxmentioning

confidence: 99%

The Promise of Pharmacogenomics in Reducing Toxicity during Acute Lymphoblastic Leukemia Maintenance Treatment

Rudin

Marable

Huang

2017

Genomics, Proteomics &Amp; Bioinformatics

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Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2–3 years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity. For both drugs, pharmacogenomic factors have been identified that could explain a large amount of the variance in toxicity between patients, and may serve as effective predictors of toxicity during the maintenance phase of ALL treatment. 6-MP toxicity is associated with polymorphisms in the genes encoding thiopurine methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), and potentially inosine triphosphatase (ITPA), which vary between ethnic groups. Moreover, MTX toxicity is associated with polymorphisms in genes encoding solute carrier organic anion transporter family member 1B1 (SLCO1B1) and dihydrofolate reductase (DHFR). Additional polymorphisms potentially associated with toxicities for MTX have also been identified, including those in the genes encoding solute carrier family 19 member 1 (SLC19A1) and thymidylate synthetase (TYMS), but their contributions have not yet been well quantified. It is clear that pharmacogenomics should be incorporated as a dosage-calibrating tool in pediatric ALL treatment in order to predict and minimize the occurrence of serious toxicities for these patients.

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SLC19A1 hot spot for MTX plasma concentration

Cited by 4 publications

References 3 publications

MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

SLC19A1 Polymorphism and Serum Methotrexate in Patients with Acute Lymphoblastic Leukemia

The Promise of Pharmacogenomics in Reducing Toxicity during Acute Lymphoblastic Leukemia Maintenance Treatment

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