<i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis. When treatment with first-line drugs fails, treatment wit...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| author | Amin Ravaei Lia Pulsatelli Elisa Assirelli Jacopo Ciaffi Riccardo Meliconi Carlo Salvarani Marcello Govoni Michele Rubini |
| author_facet | Amin Ravaei Lia Pulsatelli Elisa Assirelli Jacopo Ciaffi Riccardo Meliconi Carlo Salvarani Marcello Govoni Michele Rubini |
| author_sort | Amin Ravaei |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis. When treatment with first-line drugs fails, treatment with tumor necrosis factor-α (TNF-α) inhibitors may be prescribed to which many patients do not respond adequately, making the identification of response markers urgent. This study investigated the association of two RA-related genetic polymorphisms, c.665C>T (historically referred to as C677T) and c.1298A>C, in the <i>MTHFR</i> gene as response markers to an anti-TNF-α therapy. A total of 81 patients were enrolled, 60% of whom responded to the therapy. Analyses showed that both polymorphisms were associated with a response to therapy in an allele dose-dependent manner. The association for c.665C>T was significant for a rare genotype (<i>p</i> = 0.01). However, the observed opposite trend of association for c.1298A>C was not significant. An analysis revealed that c.1298A>C, unlike c.665C>T, was also significantly associated with the drug type (<i>p</i> = 0.032). Our preliminary results showed that the genetic polymorphisms in the <i>MTHFR</i> gene were associated with a response to anti-TNF-α therapy, with a potential significance for the anti-TNF-α drug type. This evidence suggests a role for one-carbon metabolism in anti-TNF-α drug efficacy and contributes to further personalized RA interventions. |
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| spelling | doaj.art-ddb97335a7af4141a2f159901e6e03f42023-11-16T21:09:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244411010.3390/ijms24044110<i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid ArthritisAmin Ravaei0Lia Pulsatelli1Elisa Assirelli2Jacopo Ciaffi3Riccardo Meliconi4Carlo Salvarani5Marcello Govoni6Michele Rubini7Medical Genetics Laboratory, Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, ItalyLaboratory of Immunorheumatology and Tissue Regeneration, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyMedicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyMedicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyMedicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyDivision of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, ItalySection of Hematology and Rheumatology, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, ItalyMedical Genetics Laboratory, Department of Neuroscience and Rehabilitation, University of Ferrara, 44121 Ferrara, ItalyRheumatoid arthritis (RA) is an inflammatory autoimmune disease with a prevalence of 1%. Currently, RA treatment aims to achieve low disease activity or remission. Failure to achieve this goal causes disease progression with a poor prognosis. When treatment with first-line drugs fails, treatment with tumor necrosis factor-α (TNF-α) inhibitors may be prescribed to which many patients do not respond adequately, making the identification of response markers urgent. This study investigated the association of two RA-related genetic polymorphisms, c.665C>T (historically referred to as C677T) and c.1298A>C, in the <i>MTHFR</i> gene as response markers to an anti-TNF-α therapy. A total of 81 patients were enrolled, 60% of whom responded to the therapy. Analyses showed that both polymorphisms were associated with a response to therapy in an allele dose-dependent manner. The association for c.665C>T was significant for a rare genotype (<i>p</i> = 0.01). However, the observed opposite trend of association for c.1298A>C was not significant. An analysis revealed that c.1298A>C, unlike c.665C>T, was also significantly associated with the drug type (<i>p</i> = 0.032). Our preliminary results showed that the genetic polymorphisms in the <i>MTHFR</i> gene were associated with a response to anti-TNF-α therapy, with a potential significance for the anti-TNF-α drug type. This evidence suggests a role for one-carbon metabolism in anti-TNF-α drug efficacy and contributes to further personalized RA interventions.https://www.mdpi.com/1422-0067/24/4/4110rheumatoid arthritisTNF-α inhibitorsgenetic association<i>MTHFR</i>biomarkerspharmacogenetics |
| spellingShingle | Amin Ravaei Lia Pulsatelli Elisa Assirelli Jacopo Ciaffi Riccardo Meliconi Carlo Salvarani Marcello Govoni Michele Rubini <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis International Journal of Molecular Sciences rheumatoid arthritis TNF-α inhibitors genetic association <i>MTHFR</i> biomarkers pharmacogenetics |
| title | <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis |
| title_full | <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis |
| title_fullStr | <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis |
| title_full_unstemmed | <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis |
| title_short | <i>MTHFR</i> c.665C>T and c.1298A>C Polymorphisms in Tailoring Personalized Anti-TNF-α Therapy for Rheumatoid Arthritis |
| title_sort | i mthfr i c 665c t and c 1298a c polymorphisms in tailoring personalized anti tnf α therapy for rheumatoid arthritis |
| topic | rheumatoid arthritis TNF-α inhibitors genetic association <i>MTHFR</i> biomarkers pharmacogenetics |
| url | https://www.mdpi.com/1422-0067/24/4/4110 |
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