Evaluation of the influence of polymorphisms of the transporter genes (<i>RFC1</i>, <i>MDR1</i>) and <i>GGH</i> on the efficacy of methotrexate in rheumatoid arthritis

The efficacy of methotrexate (MT) in patients with rheumatoid arthritis (RA) may be determined by genetic factors. Objective : to evaluate the isolated and combined effects single nucleotide polymorphisms (SNPs) membrane transporter proteins (RFC1 80G>A MDR1 3435C>T) GGH -401C>T gamma-glutamyl hydrolase enzyme genes on MT RA. Material methods . study group consisted 85 a confirmed diagnosis RA, who received therapy starting at 10 mg/week increasing dose maximum 25 mg/week. Efficacy was assessed after six months treatment using dynamics DAS28 index, identifying responded those did not respond therapy. Genotyping RFC1, gene performed real-time polymerase chain reaction. Three different approaches were used analyze results: 1) analysis for each genes; 2) logistic regression; 3) multifactor dimensionality reduction (MDR). Results discussion Single determine most likely predictors non-response therapy: GGH-401C>T, TT genotype (odds ratio, OR 5.09; 95% confidence interval, C11.11—23.3); forMDR13435C>T, (OR 2.38; CI0.89-6.37); RFC180G>A, - AA 1.87; CI 0.93-3.76). regression model showed significant effect homozygous -401TT low sensitivity method. multifactorial results show synergistic transport (MDR1, RFC1) encoding conversion elimination form. Conclusion Using various statistical methods, following obtained: revealed nonresponse genotype, 3435C>T RFC1 not-AA genotype; method multiple allowed -401ТТ drug method; is probably less pronounced than their effectiveness MT. SNP synergism major contributor development resistance. MDR promising that can future assess impact SNPs.