Rheumatology Advance Access originally published online on February 3, 2005
Rheumatology 2005 44(4):547-552; doi:10.1093/rheumatology/keh550
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Rheumatology Vol. 44 No. 4 © British Society for Rheumatology 2005; all rights reserved
The influence of a polymorphism at position –857 of the tumour necrosis factor 
gene on clinical response to etanercept therapy in rheumatoid arthritis
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 1 Hallym Institution for Genome Application, Hallym University Sacred Heart Hospital, Anyang and 2 Department of Internal Medicine, Division of Rheumatology, Hospital for Rheumatic Diseases, Hanyang University, Seoul, Republic of Korea.
Correspondence to: C. Kang, Department of Biological Sciences, KAIST, 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-701, Korea. E-mail: ckang{at}kaist.ac.kr; or S.-C. Bae, Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133–792, Korea. E-mail: scbae{at}hanyang.ac.kr
Objectives. We aimed to test whether polymorphisms in the etanercept target genes TNFA and LTA are associated with clinical responses to etanercept therapy in RA patients.
Methods. Clinical responses of 70 patients treated with etanercept were determined according to the ACR criteria. We genotyped 13 single-nucleotide polymorphisms (SNPs) within TNFA and LTA and tested whether they influenced the responses to 12 weeks of etanercept therapy. Univariate and multivariate analyses were performed to compare allele, genotype and haplotype distributions between responders and non-responders.
Results. Association of the –857C/T SNP at the TNFA promoter was marginally significant when patients were divided into responders and non-responders according to improvement criteria ACR20 or ACR70. When ACR70 responders (the best responders) were compared with ACR20 non-responders (the worst responders), however, the association was prominent [odds ratio (OR) = 12, 95% confidence interval (CI) = 1.4–105, P = 0.0077, Pcorrected = 0.054], as the frequency of the T allele was 5% in the ACR20 non-responders but 39% in the ACR70 responders. Moreover, the ratio of ACR70 responder number to ACR20 non-responder number among T-allele carriers was >10-fold higher than in the C-allele homozygotes (OR = 12, 95% CI = 1.2–120, P = 0.033).
Conclusions. RA patients with the T allele of TNFA –857C/T SNP respond better to etanercept therapy than homozygotes for the C allele, indicating that, when the results have been confirmed, this SNP could become a useful genetic marker for predicting responses.
KEY WORDS: Tumour necrosis factor, Rheumatoid arthritis, Etanercept, Single-nucleotide polymorphism
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