Associations Of MDR1, BCRP, MRP2 Gene Polymorphism With Refractory Rheumatoid Arthritis Drug Resistance In A Chinese Population

Objective:To investigate the association between the single nucleotide polymorphisms(SNPs)of multiple drug resistance 1(MDR1), breast cancer resistance protein(BCRP),multidrug resistance-related protein 2(MRP2) and refractory rheumatoid arthritis(RRA)drug resistance in Han Chinese population.Methods:We have screened and collected 120 cases rheumatoid arthritis(RA) patients from a multicenter clinical trial, which is designed by the department of rheumatology of the second hospital of shanxi medical university. The multicenter clinical trial trys to explore the therapeutic efficacy of methotrexate(MTX) or leflunomide(LEF) combined cyclophosphamide(CTX). The RA patients are divided into two groups according to the response to disease-modifying anti-rheumatic drugs(DMARDs). There are 41 cases in RRA group and 79 cases in single drug effective group. The SNPs of MDR1(rs1128503,rs2032582, rs1045642), BCRP(rs2231137, rs2231142) and MRP2(rs717620, rs3740066)are genotyped with SNa Pshot SNP classification technology. Genotype distribution and allele frequencies are analyzed between the two groups. We will use the chi-square, odds ratio(OR) and 95%confidence interval(95%CI) to analysis the association between 7SNPs and RRA drug resistance in Han Chinese population.Results:1. There were no statistically significant differences in gender and age between RRA group and single drug effective group.2. rs1128503, rs2032582, rs1045642, rs2231137, rs2231142, rs717620 and rs3740066 were accorded with Hardy Weinberg equilibrium.3. There were no statistical differences in genotype distribution and allele frequency between two groups(P>0.05) except the allele frequency of rs2231137(P=0.038).4. Compared to TT genotype of rs2032582, GT genotype frequency in RRA group was obviously lower than that in single drug effective group(OR=0.311, 95%CI:0.102-0.950) with a statistical differences(P<0.05). The RRA patients carried more AA genotype(P=0.030, OR=6.618, 95%CI: 1.171-3.484) and more A allele(P=0.038,OR=1.854, 95%CI: 1.032-3.331) than the RA patients, who could be cured with only single DMARD, referred to GG genotype and G allele of rs2231137. However there were no relevances between rs1128503, rs1045642, rs2231142, rs717620, rs3740066 and the risk of RRA drug resistance.Conclusion:1. rs2032582 of MDR1 gene may be associated with RRA drug resistance in Han Chinese population. GT genotype compared with TT genotype, may be a protective factor in RRA patients. However rs1128503 and rs1045642 may have nothing to do with RRA drug resistance.2. rs2231137 of BCRP gene may influence the efficacy of RA therapy with DMARDs. AA and GG genotype or A and G allele may be a risk factor to RRA, who occured multi-drug resistance(MDR). Nevertheless, BCRP rs2231142 may not increase the risk of RRA drug resistance in Han Chinese population.3. There are no relationship found in SNPs rs717620, rs3740066 of MRP2 gene.