Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population

Liu, Shuang; Fan, Huizhen; Li, Jiang; Yang, Hui; Huang, Jing; Shu, Xi; Zhang, Lu; Xu, Yuan; Li, Xiaoya; Zuo, Jieyu; Xiao, Cheng

doi:10.3389/fphar.2018.01390

Cited by 20 publications

(19 citation statements)

References 47 publications

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“…A similar trend was observed for the bio chemical parameters in psoriasis vulgaris patients, genotyped by two SNPs in MthFR gene: CTAC > CCAC > CTAA > CCAA (Table 4). Our results correspond to the data obtained by other authors, who studied the reaction of patients with rheuma toid arthritis on MTX T allele was associated with nonresponsiveness to the drug [19]. According to the litera ture data, the response of psoriasis patients to drug therapy could be determined by MthFR polymorphisms, with MthFR 677CC serving as a predictor of high drug sensitivity, and the MthFR 677 (CT, TT) and MthFR 677T1298A haplotypes serving as possible predictors of MTX adverse ef fects [13].…”

Section: Resultssupporting

confidence: 92%

Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

Fedota¹,

Roschenyuk²,

Tyzhnenko³

et al. 2020

Ukr.Biochem.J

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Section: Resultssupporting

confidence: 92%

Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

Fedota¹,

Roschenyuk²,

Tyzhnenko³

et al. 2020

Ukr.Biochem.J

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“…A total of 862 citations were collected from electronic databases, and, after excluding duplicates, screening titles and abstracts, and reading full articles, a total of 39 articles were included. 8,9,26-62 The study selection process is presented in Figure 1. The main characteristics of studies are summarized in Additional file 1: Table S1.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, the total number of patients analyzed was 161 for the MTHFR 677C>T (rs1801133) polymorphism and 157 for the ABCB1 3435C>T (rs1045642) polymorphism. 24,25…”

Section: Resultsmentioning

confidence: 99%

“…Patient recruitment and assessment have been described in detail elsewhere. 24,25 Briefly, RA patients who fulfilled the 1987 RA criteria of the American College of Rheumatology (ACR) were recruited from April 2016 to April 2018 at China–Japan Friendship Hospital and the People’s Hospital of Yichun, China. This study was registered on the Chinese Clinical Trial Registry (ChiCTR-RNC-14004887).…”

Section: Methodsmentioning

confidence: 99%

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Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis

Huang

Fan

Qiu

et al. 2020

Therapeutic Advances in Chronic Disease

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Aims: We performed an updated meta-analysis to verify correlations between gene polymorphisms and adverse events in methotrexate (MTX)-treated rheumatoid arthritis (RA) patients. Then, we conducted a retrospective cohort study of Han Chinese in China. Methods: Relevant studies were collected from the PubMed database and the EMBASE database until December 2017. Pre-allele, dominant, recessive, codominant, and homozygotic models were applied. In addition, a retrospective cohort study enrolling 162 RA patients treated with MTX was conducted. Single nucleotide polymorphism (SNP) genotyping was analyzed by PCR and product sequencing. Results: A total of 39 studies were included in 20 meta-analyses; meta-analysis showed a significant association between MTX-related toxicity and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T(rs1801133) polymorphism in East Asian RA patients, and significant associations were observed between MTX-related toxicity and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC) 347C>G (rs2372536), reduced folate carrier 1 (RFC-1) 80G>A (rs1051266), and adenosine triphosphate-binding cassette B1 (ABCB1) 3435C>T(rs1045642) polymorphisms in European RA patients but not in East Asian RA patients. Moreover, in our retrospective cohort study, ATIC 347C>G(rs2372536) and ABCB1 3435C>T(rs1045642) polymorphisms were not associated with MTX-related toxicity. However, a significant association was observed between MTX-related toxicity and RFC-1 80G>A (rs1051266) polymorphism in Chinese Han RA patients. Conclusion: Evidence-based results suggest that the MTHFR 677C>T(rs1801133), ATIC 347C>G(rs2372536), RFC-1 80G>A (rs1051266), ABCB1 3435C>T(rs1045642) polymorphisms are associated with MTX-related toxicity. Larger and more stringent study designs may provide more accurate findings for the effects of these SNPs on MTX-related toxicity, and larger sample-size studies of the Chinese Han population should be conducted for further validation.

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“…As an intermediate metabolite, tetrahydrofolate can be changed into methylenetetrahydrofolate and methyltetrahydrofolate via serine hydroxymethyl transferase 1 (SHMT1) and methylenetetrahydrofolate reductase (MTHFR), correlating to MTX hepatic toxicity ( Schmiegelow, 2009 ). There are also reports indicating that certain polymorphisms in methionine synthase reductase (MTRR) can decrease homocysteine levels and increase folate and cobalamin levels ( Lv et al, 2018 ). Additionally, solute carrier organic anion transporter 1B1 (SLCO1B1) has been described as a membrane transporter involved in the clearance of MTX ( Lopez-Lopez et al, 2011 ; Niemi et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study

Yao

et al. 2021

Front. Pharmacol.

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A study on 70 acute lymphoblastic leukemia (ALL) children (age ≤16 years) treated with high-dose methotrexate (HD-MTX) in Sichuan Provincial People’s Hospital was conducted. The aim of the study was to establish a risk-scoring model to predict HD-MTX-induced liver injury, considering gene polymorphisms’ effects. Data screening was performed through t-test, chi-square test, and ridge regression, and six predictors were identified: age, MTRR_AA, MTRR_AG, SLCO1B1_11045879_CC, albumin_1 day before MTX administration, and IBIL_1 day before MTX administration (p < 0.1). Then, the risk-scoring model was established by ridge regression and evaluated the prediction performance. In a training cohort (n = 49), the area under the curve (AUC) was 0.76, and metrics including accuracy, precision, sensitivity, specificity, positive predictive value, and negative predictive value were promising (0.86, 0.81, 0.76, 0.91, 0.81, 0.88, respectively). In a test cohort (n = 21), the AUC was 0.62 and negative predictive value was 0.80; other evaluation metrics were not satisfactory, possibly due to the limited sample size. Ultimately, the risk scores were stratified into three groups based on their distributions: low- (≤48), medium- (49–89), and high-risk (>89) groups. This study could provide knowledge for the prediction of HD-MTX-induced liver injury and reference for the clinical medication.

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Genetic Polymorphisms of TYMS, MTHFR, ATIC, MTR, and MTRR Are Related to the Outcome of Methotrexate Therapy for Rheumatoid Arthritis in a Chinese Population

Cited by 20 publications

References 47 publications

Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

Methotrexate effect on biochemical indices of psoriasis patients depends on MTHFR gene polymorphism

Are gene polymorphisms related to adverse events of methotrexate in patients with rheumatoid arthritis? A retrospective cohort study based on an updated meta-analysis

A Risk Scoring Model for High-Dose Methotrexate-Induced Liver Injury in Children With Acute Lymphoblastic Leukemia Based on Gene Polymorphism Study

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