Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy.
Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy.
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DOI：
10.1002/art.27457
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发表时间：
2010-07
影响因子：
--
通讯作者：
Plenge, Robert M.
中科院分区：
文献类型：
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作者：
Cui, Jing;Saevarsdottir, Saedis;Thomson, Brian;Padyukov, Leonid;van der Helm-van Mil, Annette H. M.;Nititham, Joanne;Hughes, Laura B.;de Vries, Niek;Raychaudhuri, Soumya;Alfredsson, Lars;Askling, Johan;Wedren, Sara;Ding, Bo;Guiducci, Candace;Wolbink, Gert Jan;Crusius, J. Bart A.;van der Horst-Bruinsma, Irene E.;Herenius, Marieke;Weinblatt, Michael E.;Shadick, Nancy A.;Worthington, Jane;Batliwalla, Franak;Kern, Marlena;Morgan, Ann W.;Wilson, Anthony G.;Isaacs, John D.;Hyrich, Kimme;Seldin, Michael F.;Moreland, Larry W.;Behrens, Timothy W.;Allaart, Cornelia F.;Criswell, Lindsey A.;Huizinga, Tom W. J.;Tak, Paul P.;Bridges, S. Louis, Jr.;Toes, Rene E. M.;Barton, Anne;Klareskog, Lars;Gregersen, Peter K.;Karlson, Elizabeth W.;Plenge, Robert M.
抗肿瘤坏死因子α（抗TNF）治疗是类风湿关节炎（RA）的主要治疗方法。本研究的目的是检测已确定的RA遗传危险因素，以确定是否相同的等位基因也影响抗TNF治疗的反应。在9个不同RA队列的国际合作联盟中，共研究了1,283例接受依那西普、英夫利西单抗或阿达木单抗治疗的RA患者。主要终点比较了根据欧洲抗风湿联盟（EULAR）反应标准具有良好治疗反应的RA患者（n = 505）与被认为无反应的RA患者（n = 316）。次要终点是根据28个关节的疾病活动性评分（Δ DAS 28），疾病活动性水平较基线的变化。测试了年龄、性别和合并用药等临床因素是否可能与治疗反应相关。31个单核苷酸多态性（SNPs）与RA的风险进行了基因分型，并测试与治疗反应的任何关联，使用单变量和多变量逻辑回归模型。在31个RA相关风险等位基因中，PTPRC（也称为CD 45）基因位点（rs 10919563）的SNP与主要终点相关，即EULAR良好反应与无反应（多变量模型中比值比[OR] 0.55，P = 0.0001）。使用次要终点Δ DAS 28获得了相似的结果（P = 0.0002）。有证据表明，与自身抗体阴性患者（OR 0.90，95% CI 0.41-1.99）相比，自身抗体阳性患者与RA的关联性更强（OR 0.55，95%置信区间[95% CI] 0.39-0.76）。在PTPRC基因位点上，抗TNF治疗反应与RA风险等位基因之间存在统计学显著相关性。需要进行额外的研究，以在其他患者样本中复制这一发现。
Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections.
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影响因子：
--
作者：
Lee, Yvonne C.;Raychaudhuri, Soumya;Cui, Jing;De Vivo, Immaculata;Ding, Bo;Alfredsson, Lars;Padyukov, Leonid;Costenbader, Karen H.;Selelstad, Mark;Graham, Robert R.;Klareskog, Lars;Gregersen, Peter K.;Plenge, Robert M.;Karlson, Elizabeth W.
通讯作者：
Karlson, Elizabeth W.
影响因子：
--
作者：
Goekoop-Ruiterman, YPM;de Vries-Bouwstra, JK;Dijkmans, C
通讯作者：
Dijkmans, C
影响因子：
30.8
作者：
Barton A;Thomson W;Ke X;Eyre S;Hinks A;Bowes J;Plant D;Gibbons LJ;Wellcome Trust Case Control Consortium;YEAR Consortium;BIRAC Consortium;Wilson AG;Bax DE;Morgan AW;Emery P;Steer S;Hocking L;Reid DM;Wordsworth P;Harrison P;Worthington J
通讯作者：
Worthington J
影响因子：
30.8
作者：
Gregersen, Peter K.;Amos, Chistopher I.;Lee, Annette T.;Lu, Yue;Remmers, Elaine F.;Kastner, Daniel L.;Seldin, Michael F.;Criswell, Lindsey A.;Plenge, Robert M.;Holers, V. Michael;Mikuls, Ted R.;Sokka, Tuulikki;Moreland, Larry W.;Bridges, S. Louis, Jr.;Xie, Gang;Begovich, Ann B.;Siminovitch, Katherine A.
通讯作者：
Siminovitch, Katherine A.
影响因子：
5.5
作者：
Hyrich, K. L.;Watson, K. D.;Symmons, D. P. M.
通讯作者：
Symmons, D. P. M.