Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype and methotrexate-induced adverse events in South Indian Tamil rheumatoid arthritis.

Autor: Muralidharan N; Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry, 605 006, India., Antony PT, Jain VK, Mariaselvam CM, Negi VS
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2015 Aug; Vol. 71 (8), pp. 959-65. Date of Electronic Publication: 2015 Jun 14.
DOI: 10.1007/s00228-015-1885-0
Abstrakt: Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily targeting the synovial joints causing joint damage and significant functional impairment. Methotrexate (MTX) remains the mainstay for the treatment of RA, and approximately 10-30% of the patients fail to attain remission because of inefficacy of the drug or due to development of adverse events. Multidrug resistance 1 (MDR1) gene encodes for permeable glycoprotein (P-gp) which is an integral membrane protein for the transport of chemotherapeutic agents, immunosuppressive drugs etc. MDR1 3435C>T results in a wobble mutation in exon 26 but is associated with altered P-gp expression and reduced P-gp function. The present study was carried out to find the role of MDR1 3435C>T gene polymorphism with clinical phenotype, treatment response, and MTX adverse events in 336 RA and 329 healthy controls of South Indian Tamil ethnicity.
Methods: MDR1 3435C>T gene polymorphism was analyzed by TaqMan 5' nuclease assay.
Results: We found MDR1 3435T allele as a risk allele for contributing to high EULAR disease activity [p = 0.02, OR 1.50, 95% CI (1.06-2.13)]. Also, MDR1 3435CT genotype was associated with deforming disease [p = 0.02, OR 1.79, 95% CI (1.11-2.88)]. However, this SNP did not influence the MTX treatment response in these patients. MDR1 3435CT genotype was associated with MTX-induced adverse events [p = 0.01, OR 2.01, 95% CI (1.15-3.52)], and the 3435 TT genotype remained protective for the development of adverse events [p = 0.009, OR 0.40, 95% CI (0.21-0.78)]. Also, the heterozygous 3435 CT genotype was associated with gastrointestinal events [p = 0.02, OR 3.62, 95% CI (1.25-10.47)], and CT genotype remained protective in patients developing infection [p = 0.002, OR 0.05, 95% CI (0.006-0.460)].
Conclusion: MDR1 3435C>T gene polymorphism influences the clinical phenotype and adverse events to MTX in the South Indian cohort of patients with RA.
Databáze: MEDLINE
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