title: Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outcome in south Indian Tamil patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease causing joint damage and significant functional impairment. Methotrexate (MTX) remains the mainstay for the treatment of RA. MTX inhibits several enzymes of the folate and nucleotide pathways. Thymidylate synthase (TYMS) is an important enzyme in the de novo pyrimidine pathway responsible for DNA replication. The two common gene polymorphisms analyzed in TYMS are 28-bp tandem repeat polymorphism and a 6-bp insertion/deletion polymorphism. The present study was carried out to find the role of these TYMS gene polymorphisms with clinical phenotype, treatment response, and MTX adverse events in 254 patients with RA of south Indian Tamil ethnicity. TYMS gene polymorphisms were analyzed by PCR. The allele frequencies of TYMS gene polymorphisms did not differ between good and non-responders. However, the TYMS 28-bp tandem repeat 3R allele was higher in non-responders than in patients undergoing remission [64 vs 51.11%, p = 0.06, OR 0.58, 95% CI (0.34-1.00)]. The TYMS 6-bp deletion allele was higher in non-responders than good responders [78.20 vs 64.92%, p = 0.06, OR 0.51 95% CI (0.27-0.98)]. TYMS 3R allele and TYMS 6-bp deletion allele may favor non-response to MTX in south Indian Tamils. TYMS gene polymorphisms did not influence MTX adverse events.
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Niveditha
authors.initials: N
authors.lastname: Muralidharan
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Durga P
authors.initials: DP
authors.lastname: Misra
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India.
authors.forename: Vikramraj K
authors.initials: VK
authors.lastname: Jain
authors.affiliation: Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India. vsnegi22@yahoo.co.in.
authors.forename: Vir Singh
authors.initials: VS
authors.lastname: Negi
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D007194:India; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D013940:Thymidylate Synthase; D008727:Methotrexate
keywords: Methotrexate; Rheumatoid arthritis; South Indian; Thymidylate synthase; Treatment response