류마티스 관절염 환자에서 HLA-DRB1의 유전적 변이와Etanercept 치료 반응과의 연관성: 예비 연구

Abstract

Objective: To investigate the roles of genetic variation in the HLA-DRB1 as predictors of response to etanercept treatment in rheumatoid arthritis (RA) patients. Methods: Clinical responses of 66 patients treated with etanercept were determined according to the ACR criteria (ACR20 and 70). HLA-DRB1 typing and further subtyping of all alleles were performed by polymerase chain reaction, sequence-specific oligonucleotide probe hybridization, and direct DNA sequencing analysis. We tested whether genetic variation in the HLA-DRB1 influenced on the responses to 12 weeks of etanercept therapy. Univariate and multivariate analyses were performed to compare allele and genotype distribution between responders and nonresponders. Results: When allelic association with etanercept response was analyzed with ACR20 and ACR 70 criteria for shared epitope alleles (HLA-DRB1 *0101, *0401, *0404, *0405, *0410, *1001,and *1406 alleles) and protective alleles (HLA-DRB1*0701, *0802, *1301, *1302, *1403, and *1405 alleles), there was no association with etanercept efficacy. When ACR20 nonresponders were compared with ACR70 responders, there was no significant association. Next, we tested genotypic association for shared epitope carriage status. The presence of HLA-DRB1 alleles encoding the shared epitope (1 and 2 copies) was marginally associated with nonresponse effect for ACR 70 response (OR=0.27, 95% CI=0.08～0.93, P=0.045). Conclusion: There was no influence of genetic variation in the HLA-DRB1 on the response to treatment of RA with etanercept.