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

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 5'nuclease 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.
AuthorsNiveditha Muralidharan, Rajan Sundaram, Sunitha Kodidela, K G Chengappa, Christina Mary Mariaselvam, Durga P Misra, Vir S Negi
JournalThe pharmacogenomics journal (Pharmacogenomics J) Vol. 20 Issue 2 Pg. 342-349 (04 2020) ISSN: 1473-1150 [Electronic] United States
PMID31611592 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antirheumatic Agents
  • Peptide Synthases
  • folylpolyglutamate synthetase
  • Methotrexate
Topics
  • Adult
  • Antirheumatic Agents (adverse effects)
  • Arthritis, Rheumatoid (drug therapy, epidemiology, genetics)
  • Female
  • Gastrointestinal Diseases (chemically induced, epidemiology)
  • Humans
  • India (epidemiology)
  • Male
  • Methotrexate (adverse effects)
  • Middle Aged
  • Peptide Synthases (genetics)
  • Polymorphism, Single Nucleotide (genetics)
  • Prospective Studies

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