Evaluation of TRAF6 in a large multiancestral lupus cohort.
Evaluation of TRAF6 in a large multiancestral lupus cohort.
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DOI：
10.1002/art.34361
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发表时间：
2012-06
影响因子：
--
通讯作者：
Bae, Sang-Cheol
中科院分区：
文献类型：
--
作者：
Namjou, Bahram;Choi, Chan-Bum;Harley, Isaac T. W.;Alarcon-Riquelme, Marta E.;Kelly, Jennifer A.;Glenn, Stuart B.;Ojwang, Joshua O.;Adler, Adam;Kim, Kwangwoo;Gallant, Caroline J.;Boackle, Susan A.;Criswell, Lindsey A.;Kimberly, Robert P.;Brown, Elizabeth E.;Edberg, Jeffrey;Alarcon, Graciela S.;Stevens, Anne M.;Jacob, Chaim O.;Gilkeson, Gary S.;Kamen, Diane L.;Tsao, Betty P.;Anaya, Juan-Manuel;Kim, Eun-Mi;Park, So-Yeon;Sung, Yoon-Kyoung;Guthridge, Joel M.;Merrill, Joan T.;Petri, Michelle;Ramsey-Goldman, Rosalind;Vila, Luis M.;Niewold, Timothy B.;Martin, Javier;Pons-Estel, Bernardo A.;Vyse, Timothy J.;Freedman, Barry I.;Moser, Kathy L.;Gaffney, Patrick M.;Williams, Adrienne H.;Comeau, Mary E.;Reveille, John D.;Kang, Changwon;James, Judith A.;Scofield, R. Hal;Langefeld, Carl D.;Kaufman, Kenneth M.;Harley, John B.;Bae, Sang-Cheol
系统性红斑狼疮（SLE）是一种异质性自身免疫性疾病，由于复杂的遗传和环境因素，导致显著的免疫系统异常。TRAF 6是SLE的候选基因，其在对免疫和器官发育重要的几个信号通路中起主要作用。在来自不同祖先的7，490名SLE和6，780名对照受试者中评估了TRAF 6的15个单核苷酸多态性（SNP）。进行了基于人群的病例对照关联分析和荟萃分析。计算P值、错误发现率q值和比值比以及95%置信区间。检测到多个SNP的关联证据。SNPs rs 5030437和rs 4755453获得了最佳的总体p值（分别为p=7.85×10−5和p=4.73×10−5），在人群中没有显著的异质性（Q统计中p=0.67和p=0.50）。此外，先前报道的与RA相关的rs 540386被发现与这两个SNP在LD中（r2= 0.95），并证明与SLE以相同方向相关的证据（荟萃分析p=9.15×10−4，OR=0.89，95%CI=0.83-0.95）。血小板减少改善了不同人群的总体结果（rs 5030470的荟萃分析p=1.99×10−6，OR=0.57，95%CI=0.45-0.72）。最后，在显性模型下，在一个可用的SNP rs 5030437中检测到34个非洲裔美国人家系中存在血小板减少症的基于家族的关联证据，Z评分幅度为2.28（p=0.02）。我们的数据表明TRAF 6与SLE的相关性与先前的RA相关性报告一致。这些数据进一步支持TRAF 6参与自身免疫的发病机制。
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. TRAF6 is a candidate gene for SLE, which has a major role in several signaling pathways that are important for immunity and organ development. Fifteen single-nucleotide polymorphisms (SNPs), across TRAF6 were evaluated in 7,490 SLE and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. Evidence of associations in multiple SNPs was detected. The best overall p values were obtained for SNPs rs5030437 and rs4755453 (p=7.85×10−5 and p=4.73×10−5, respectively) without significant heterogeneity among populations (p=0.67 and p=0.50 in Q-statistic). In addition, rs540386 previously reported to be associated with RA was found to be in LD with these two SNPs (r2= 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis p=9.15×10−4, OR=0.89, 95%CI=0.83–0.95). Thrombocytopenia improved the overall results in different populations (meta-analysis p=1.99×10−6, OR=0.57, 95%CI=0.45–0.72, for rs5030470). Finally evidence of family based association in 34 African-American pedigrees with the presence of thrombocytopenia were detected in one available SNP rs5030437 with Z score magnitude of 2.28 (p=0.02) under a dominant model. Our data indicate the presence of association of TRAF6 with SLE in agreement with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity.
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影响因子：
5.2
作者：
Horvath, S;Xu, X;Laird, NM
通讯作者：
Laird, NM
影响因子：
11.4
作者：
Schultheiss, U;Püschner, S;Kieser, A
通讯作者：
Kieser, A
影响因子：
2.6
作者：
Cooper, GS;Parks, CG;Dooley, MA
通讯作者：
Dooley, MA
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
6q23 上 TNFAIP3 附近的遗传变异与系统性红斑狼疮相关。
影响因子：
30.8
作者：
Graham, Robert R.;Cotsapas, Chris;Davies, Leela;Hackett, Rachel;Lessard, Christopher J.;Leon, Joanlise M.;Burtt, Noel P.;Guiducci, Candace;Parkin, Melissa;Gates, Casey;Plenge, Robert M.;Behrens, Timothy W.;Wither, Joan E.;Rioux, John D.;Fortin, Paul R.;Graham, Deborah Cunninghame;Wong, Andrew K.;Vyse, Timothy J.;Daly, Mark J.;Altshuler, David;Moser, Kathy L.;Gaffney, Patrick M.
通讯作者：
Gaffney, Patrick M.