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Folyl polyglutamate synthethase (FPGS) gene polymorphisms may influence methotrexate adverse events in South Indian Tamil Rheumatoid Arthritis patients

The Pharmacogenomics Journal volume 20, pages 342–349 (2020)Cite this article

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Abstract

The aim of the study was to look for the association of FPGS 2752 G > A (rs1544105), FPGS 1994 A > G (rs10106), and GGH 452 C > T (rs 11545078), GGH −401C > T (rs 3758149) gene polymorphisms with methotrexate (MTX) treatment response and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). Further the influence of these gene polymorphisms on MTX polyglutamate levels was analyzed. A total of 330 patients with RA were investigated. FPGS gene polymorphisms were analyzed by TaqMan 5ʹnuclease assay and GGH gene polymorphisms were analyzed by PCR-RFLP. Methotrexate polyglutamates (nmol/L of packed erythrocytes) were measured by liquid chromatography mass spectrometry (LCMS/MS) method. We found that the heterozygous genotype of FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15–3.35)] and FPGS rs10106 AG genotype [p = 0.01, OR 2.11, 95% CI (1.20–3.71)] were associated with MTX adverse events. FPGS rs1544105 and GGH −401C > T SNPs influenced the polyglutamate levels. None of the investigated SNPs seems to be associated with MTX treatment outcome.

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Acknowledgements

The study was supported by an intramural research grant by JIPMER, Puducherry, India. In addition the infrastructure and other support provided by DST-FIST and ICMR-INSERM programs are also acknowledged.

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Authors and Affiliations

  1. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Niveditha Muralidharan, K. G. Chengappa, Christina Mary Mariaselvam, Durga P. Misra & Vir S. Negi

  2. Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India

    Rajan Sundaram & Sunitha Kodidela

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  1. Niveditha Muralidharan
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Contributions

VSN conceived, planned, and coordinated the study. NM performed the laboratory work with the precious help of CMM, RS, and SK. NM performed statistical analysis.VSN, DPM, and CKG recruited the patients, collected, organized, and interpreted the clinical data. VSN and NM wrote the manuscript. DPM, CMM, and CKG critically reviewed the manuscript. VSN takes the primary responsibility for the article.

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Correspondence to Vir S. Negi.

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The study was carried out in compliance with international, national, and institutional regulations. Institute Ethics committee has approved the study. All persons gave informed consent prior to the inclusion in the study.

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Muralidharan, N., Sundaram, R., Kodidela, S. et al. Folyl polyglutamate synthethase (FPGS) gene polymorphisms may influence methotrexate adverse events in South Indian Tamil Rheumatoid Arthritis patients. Pharmacogenomics J 20, 342–349 (2020). https://doi.org/10.1038/s41397-019-0097-x

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