Association of the MDR1 gene polymorphisms in refractory rheumatoid arthritis patients: an analysis

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  Objective: the genetic polymorphisms of the ABCB1 (ATP-binding cassette B1) gene influence the function of its product, P-gp, which acts as a efflux pump that transports a large variety of substrates and have been proposed to be associated with pharmacological response of rheumatoid arthritis (RA).In this study, we evaluate whether the two single nucleotide polymorphisms (G2677T/A and C 1236T) in the ABCB 1 gene were associated with refractory RA in a Chinese population, Methods: a total of 204 patients with rheumatoid arthritis who had been treated with more than two disease-modifying antirheumatic drugs (DMARDs) for at least half a year.Of this patent group 112 were drug responsive and 92 were drug resistant according to the remission criteria of the American college of rheumatology (ACR20).Genotypes of G2677T/A and C1236T were detected in 104 age-and sex-matched normal people and 204 RA patients using the polymerase chain reaction followed by restriction digestion (PCR-RFLP).Normal population sample populace from the same ethnicity and territory was genotyped to check for population stratification.The genotype and allele frequencies of MDR1 polymorphisms were compared between drug-resistant and drug-responsive subjects.Results: compared to responders and controls, the nonresponders carried more 2677TT genotype (x2=12.781, P=0.002).But no significant differences were observed in allelic and haplotypic frequencies of ABCB1 polymorphisms between patients with drug-resistant and drug-responsive subjects.Conclusion: ABCB1 gene polymorphism may not be related with the RA susceptibility, but may influence the efficacy of RA therapy with DMARDs, and the 2677TT genotype may be related with refractory RA.
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