The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate efficacy or methotrexate related-toxicity in rheumatoid arthritis: A meta-analysis

Li, Xiaobing; Hu, MingCai; Li, Wanping; Gu, Li; Chen, MeiJuan; Ding, Huihua; Vanarsa, Kamala; Du, Yong

doi:10.1016/j.intimp.2016.05.012

Cited by 39 publications

(22 citation statements)

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“…Moreover, stratification by ethnicity identified a significant association between the RFC-1 80G > A (rs1051266) allele frequency (GG, GA and AA) and MTX response status in Europeans in pre-allele, recessive and homozygotic model, and South Asian populations in pre-allele, dominant model and homozygotic model. This result was consistent with two previous meta-analyses, which found that the RFC-1 80G > A polymorphism is associated with responsiveness to MTX therapy12, even though the inclusion and exclusion criteria are different. In the present study, we only focused on the association between gene polymorphisms and the response to MTX monotherapy in RA patients and did not investigate toxicity28 and gene-gene interactions29.…”

Section: Discussionsupporting

confidence: 92%

“…Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovial joint inflammation, which leads to disability and diminished quality of life12. The main objectives for managing RA are to control pain, prevent or control joint damage and avoid long-term loss of function.…”

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confidence: 99%

“…Over the past 10 years, seven meta-analyses1235121314 on the association between polymorphisms and the clinical efficacy of MTX in RA patients were published in the PubMed and Embase databases. To the best of our knowledge, this is the first systematic review (SR) summarizing all of the available studies on the association between SNPs or VNTR polymorphisms and responsiveness to MTX in RA patients.…”

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confidence: 99%

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Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Qiu

Huang

Shu

et al. 2017

Sci Rep

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Methotrexate (MTX) is widely used and considered a first-line disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX effectiveness in RA patients, although inconsistent results have been reported. A systematic review and meta-analysis were performed to identify genetic variants associated with MTX efficacy. A total of 30 publications that included 34 genes and 125 SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the systematic review (SR), and 21 studies were included in 9 meta-analyses. Associations between MTX response in RA patients in MTHFR 1298A > C (rs1801131), ATIC 347C > G (rs2372536), RFC-1 80G > A (rs1051266), SLC19A1 A > G (rs2838956) and SLC19A1 G > A (rs7499) genetic polymorphisms were found, but not observed between the MTHFR 677C > T (rs1801133), TYMS 28 bp VNTR (rs34743033), MTRR 66A > G (rs1801394), and ABCB1 3435C > T (rs1045642). However, for the polymorphisms not being associated following meta-analysis could still be associated if larger cohorts were used, and studies of other polymorphisms are necessary in large cohorts and a rigorous way, which may provide more accurate results for the effect of the gene polymorphisms on the MTX response.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

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confidence: 99%

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Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Qiu

Huang

Shu

et al. 2017

Sci Rep

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“…[1,2] The main objectives for managing RA are to control pain, prevent or control joint damage, and avoid long-term loss of function. Disease-modifying antirheumatic drugs (DMARDs) are mainstay treatments for controlling the symptoms of RA and modifying its radiographic progression.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis

et al. 2017

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Background:Methotrexate (MTX) is widely used and considered a first-line disease modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). However, 10% to 30% of patients discontinue therapy within a year of starting the treatment, usually because of undesirable side effects. Many of the relevant genes have been investigated to estimate the association between gene polymorphisms and MTX toxicity in RA patients, although inconsistent results have been reported.Methods:We searched EMBASE and PubMed in February 2016 for polymorphisms and pharmacogenomics study of the toxicity of MTX monotherapy in RA patients. The meta-analysis was stratified by whether genetic variants associated with MTX toxicity.Results:A total of 42 publications that included 28 genes with 88 gene SNPs associated with the transporters, enzymes, and metabolites of MTX or the progression of RA were included in the SR, and 31 studies were included in 7 meta-analyses. The meta-analysis showed a significant association between the toxicity of MTX and the RFC-1 80G > A (rs1051266) polymorphism in the European RA patients.Conclusion:RFC-1 80G > A (rs1051266) polymorphism was associated with MTX toxicity, and larger and more stringent study designs may provide more accurate results for the effect of these SNPs on the MTX toxicity.

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“…The frequency of the T allele of MTHFR is 36.9%, 41.7%, 58.6% and 8.1%, in Japan, the USA, Mexico and Indonesia, respectively (Sadewa et al 2002). The authors also tested the following high frequency SNPs affecting folate and homocysteine metabolism (Hiraoka et al 2004): MTHFR A1298C, CBS844ins68 (cystathionine‐β‐synthase), MS A2756G (methionine synthase) (Cai et al 2014), MTRR A66G (methionine synthase reductase) (Zhi et al 2016), and RFC‐1 G80A (reduced folate carrier‐1) (Li et al 2016a). CBS844ins68 is the 8th exon insertion mutation and comprises 68 base pairs (Cai et al 2014).…”

Section: Genetic Polymorphisms Of Folate Metabolismmentioning

confidence: 99%

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification

Kagawa

Hiraoka

Kageyama

et al. 2017

Congenital Anomalies

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The introduction of mandatory fortification of grains with folate in 1998 in the United States resulted in 767 fewer spina bifida cases annually and a cost saving of $603 million per year. However, far more significant medical cost savings result from preventing common diseases, including myocardial infarction, stroke, dementia and osteoporosis. A cost‐effectiveness analysis showed a gain of 266 649 quality‐adjusted life‐years and $3.6 billion saved annually, mainly due to the reduction of cardiac infarction. The recommended folate intake in Japan is 240 μg/day whereas it is 400 μg/day internationally. Our Sakado Folate Project targeted individuals with genetic polymorphism of methylenetetrahydrofolate reductase or with hyperhomocysteinemia. Using, for example, folate‐fortified rice, resulted in an increase in serum folate and a decrease in serum homocysteine in the participants, and reduced medical costs were achieved by decreasing myocardial infarction, stroke, dementia and fracture. Due to the small population of Sakado City (approximately 101 000) and small number of births (693) in 2015, a decrease in spina bifida could not be confirmed but there was a significant decrease in the number of very low birthweight infants. The genome notification of subjects was effective in motivating intake of folate, but the increase in serum folate (from 17.4 to 22.5 nmol/L, 129%) was less than that observed following compulsory folic acid fortification of cereals in the USA (from 12.1 to 30.2 nmol/L, 149.6%). Mandatory folic acid fortification is cheap in decreasing medical costs and is thus recommended in Japan.

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The association between reduced folate carrier-1 gene 80G/A polymorphism and methotrexate efficacy or methotrexate related-toxicity in rheumatoid arthritis: A meta-analysis

Cited by 39 publications

References 43 publications

Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Polymorphisms and Pharmacogenomics for the Clinical Efficacy of Methotrexate in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-analysis

Polymorphisms and pharmacogenomics for the toxicity of methotrexate monotherapy in patients with rheumatoid arthritis

Medical cost savings in Sakado City and worldwide achieved by preventing disease by folic acid fortification

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