Are Gene Polymorphisms Related to Treatment Outcomes of Methotrexate in Patients with Rheumatoid Arthritis? A Systematic Review and Meta-analysis

Chen, Yuehong; Zou, Kun; Sun, Jianhong; Yang, Yuan; Liu, Gang

doi:10.2217/pgs-2016-0158

Cited by 29 publications

(21 citation statements)

References 80 publications

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“…Despite the lack of association between rs2372536 polymorphism and the MTX treatment response in some studies, other studies, including meta‐analyses, support the association between rs2372536 polymorphism and MTX response status in some populations . Moreover, another SNP in this gene (ATIC T675C [rs4673993]) may possibly predict responsiveness to MTX in RA patients …”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

“…In addition to SNPs on the MTHFR and ATIC genes, several other SNPs also have been reported to be associated with MTX responsiveness. For example, the association between the IL1B and IL1RN polymorphisms, KIR2DS2 and KIR2DL2, CHST11, SLC19A1 A > G (rs2838956) and AMPD1 34C > T and the response to MTX in RA patients has been detected. TYMS, an important enzyme in the de novo pyrimidine pathway responsible for DNA replication is also probably involved in treatment with MTX.…”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

“…Studies have shown that MTHFR is associated with MTX responsiveness and to MTX‐related toxicity. Chen et al conducted a meta‐analysis and concluded that the presence of MTHFR C677T and the absence of FPGS rs10106 can predict adverse events in RA patients treated with MTX. In other words, MTHFR C677T was associated with presenting overall adverse reactions in allelic, recessive and dominant models.…”

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

“…123,133,134 Moreover, another SNP in this gene (ATIC T675C [rs4673993]) may possibly predict responsiveness to MTX in RA patients. 135 In addition to SNPs on the MTHFR and ATIC genes, several other SNPs also have been reported to be associated with MTX responsiveness. For example, the association between the IL1B and IL1RN polymorphisms, 111 KIR2DS2 and KIR2DL2, 32 CHST11, 136 SLC19A1 A > G (rs2838956) 123 and AMPD1 34C > T 135 and the response to MTX in RA patients has been detected.…”

Section: Methotrexatementioning

confidence: 99%

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Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

2018

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For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed.

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Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

Section: Current Knowledge About Pharmacogenetics Of Adsmentioning

confidence: 99%

Section: Methotrexatementioning

confidence: 99%

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Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases

2018

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“…12 As reported, several studies indicated that the polymorphisms of these above genes had significant impacts on the efficacy of MTX in vivo. [13][14][15][16][17] However, the influence of these gene polymorphisms has not been reported in the Chinese psoriatic population. Therefore, this study aims to explore the relationship between genetic variations and the efficacy of MTX in the Chinese psoriasis patients, which may provide a theoretical basis for further precise clinical MTX treatment in the Chinese psoriatic population.…”

Section: Introductionmentioning

confidence: 99%

The impacts of gene polymorphisms on methotrexate in Chinese psoriatic patients

Chen

et al. 2020

Acad Dermatol Venereol

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Background Methotrexate (MTX) is the first‐line treatment for psoriasis in China. The metabolic processes of MTX include various proteins and genes. Previous studies have shown that gene polymorphisms had significant impacts on the efficacy of MTX. However, the influence of gene polymorphisms has not been reported in the Chinese psoriatic patients. Objective The aim of this study was to verify the impacts of candidate genes polymorphisms on the effectiveness of MTX in a Chinese psoriatic population. Methods In this study, we enrolled 259 psoriasis patients from two clinical centres. Each of them received MTX treatment at 7.5–15 mg/week for at least 8 weeks. Patients were stratified as responders and non‐responders according to whether the Psoriasis Area and Severity Index score declined more than 75% (PASI75). According to previous reports, 16 single nucleotide polymorphisms (SNPs) were selected and genotyped for each patient using the Sequenom platform. Fisher’s exact test, the chi‐square test, Mann–Whitney tests and ANOVA analyses were used for statistical analysis. Results Among 259 patients, there were 182 males and 77 females, 63 patients with psoriatic arthritis and 196 patients without arthritis phenotype, and the age of all patients ranged from 19 to 70 years (49.7 ± 13.6). The baseline PASI value of patients was 13.8 ± 8.5, and 33.2% of patients achieved a PASI75 response after MTX treatment. Patients carrying the ATP‐binding cassette subfamily B member 1 gene (ABCB1) rs1045642 TT genotype were associated with more severe psoriasis skin lesion (P = 0.032). Furthermore, the ABCB1 rs1045642 TT genotype was found to be more frequent in non‐responders (P = 0.017), especially in moderate‐to‐severe patients (P = 0.002) and patients without psoriatic arthritis (P = 0.026) after MTX treatment. Conclusion We have demonstrated for the first time that polymorphism of the ABCB1 rs1045642 TT genotype is predictive of a worse clinical response of skin lesions to MTX therapy in a Chinese psoriatic population.

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