The C677T polymorphism in the<i>MTHFR</i>gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population

Cáliz, Rafael; Amo, Jokin del; Balsa, Alejandro; Blanco, Francisco J.; Silva, L; Sanmarti, Raimón; Martinez, FG; Collado,; Ramirez, M del Carmen; Tejedor, Diego; Artieda, Marta; Pascual‐Salcedo, Dora; Oreiro, N.; Andreu, José Luís; Graell, Eduard; Simón, Laureano; Martínez, Antonio; Mulero, Juan

doi:10.3109/03009742.2011.617312

Cited by 54 publications

(33 citation statements)

References 26 publications

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“…Although MTHFR genetic polymorphism have been implicated in MTX-induced toxicities in adults with breast cancer [16] and rheumatoid arthritis [17], as for adults with hematological malignancy, the results of relevant studies remain inconsistent and even conflicting. Considering the different study designs and insufficient power of individual studies, we conducted the present meta-analysis in order to provide a comprehensive and reliable conclusion with less random error and more precise estimates.…”

Section: Discussionmentioning

confidence: 99%

MTHFR Gene Polymorphisms and Methotrexate Toxicity in Adult Patients with Hematological Malignancies: A Meta-Analysis

Zhao

Liang

et al. 2016

Pharmacogenomics

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Section: Discussionmentioning

confidence: 99%

MTHFR Gene Polymorphisms and Methotrexate Toxicity in Adult Patients with Hematological Malignancies: A Meta-Analysis

Zhao

Liang

et al. 2016

Pharmacogenomics

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“…This theory, however, lacks conclusive proof. Cáliz et al demonstrated that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population [20]. Single nucleotide polymorphisms (SNP) in the genes encoding enzymes in the MTX cellular pathway have been implicated in determining both MTX efficacy and toxicity [21].…”

Section: Discussionmentioning

confidence: 99%

Methotrexate-Associated Nonalcoholic Fatty Liver Disease with Transaminitis in Rheumatoid Arthritis

Sakthiswary

Chan

Koh

et al. 2014

The Scientific World Journal

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Background. The aim of this study was to determine the risk factors of MTX-associated nonalcoholic fatty liver disease (NAFLD) with transaminitis in a cohort of rheumatoid arthritis (RA) patients from Singapore. Methods. Patients who developed ultrasound proven NAFLD with transaminitis while on MTX therapy were identified. The demographic and clinical characteristics of the above patients (cases) were compiled and compared with age- and gender-matched controls who were RA patients on long standing MTX therapy without any episode of transaminitis. Results. Among the 978 patients who had received MTX, the prevalence of MTX-associated NAFLD was 4.7% (46 patients). Compared to the controls, the cases had significantly higher mean cumulative dose of MTX (4.03 ± 2.25 g versus 10.04 ± 9.94 g, P ≤ 0.05), weekly dose of MTX (11.3 ± 4.8 mg versus 13.1 ± 4.4 mg weekly, P = 0.033), and fasting blood glucose (P = 0.029). Following multivariate regression analysis, only cumulative dose of MTX remained significant (P = 0.015). Among the cases, the cumulative dose of MTX was found to have a significant positive correlation with the alanine transaminase (ALT) level (P < 0.05, standardised beta coefficient 0.512). Conclusion. The cumulative dose of MTX was the only independent predictor of MTX-associated NAFLD with transaminitis.

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“…Patiño-García et al31 observed that among their osteosarcoma patients population, 677 T and 1298 T were more frequent in higher grade of gastrointestinal and hematologic toxicities. Cáliz et al40 also concluded that for rheumatoid arthritis patients that C677T polymorphism harbors suffered increased MTX toxicity. Similar results were reported by Yang et al…”

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confidence: 99%

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate

et al. 2015

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Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

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The C677T polymorphism in theMTHFRgene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population

Abstract: These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.

Cited by 54 publications

References 26 publications

MTHFR Gene Polymorphisms and Methotrexate Toxicity in Adult Patients with Hematological Malignancies: A Meta-Analysis

MTHFR Gene Polymorphisms and Methotrexate Toxicity in Adult Patients with Hematological Malignancies: A Meta-Analysis

Methotrexate-Associated Nonalcoholic Fatty Liver Disease with Transaminitis in Rheumatoid Arthritis

Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate

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