Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.
Further evidence of subphenotype association with systemic lupus erythematosus susceptibility loci: a European cases only study.
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DOI：
10.1371/journal.pone.0045356
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
European Consortium of SLE DNA Collections
中科院分区：
文献类型：
--
作者：
Alonso-Perez E;Suarez-Gestal M;Calaza M;Ordi-Ros J;Balada E;Bijl M;Papasteriades C;Carreira P;Skopouli FN;Witte T;Endreffy E;Marchini M;Migliaresi S;Sebastiani GD;Santos MJ;Suarez A;Blanco FJ;Barizzone N;Pullmann R;Ruzickova S;Lauwerys BR;Gomez-Reino JJ;Gonzalez A;European Consortium of SLE DNA Collections
系统性红斑狼疮（SLE）表现出一系列的临床表现，使其诊断，治疗和研究变得复杂。这种变异性可能与环境暴露和遗传因素有关，其中已知的SLE易感基因位点是主要候选者。第一次发表的分析似乎表明，这是其中一些情况下，但结果仍然是不确定的，我们的目的是进一步探讨这个问题。分析了来自10个国家17个中心招募的1444例欧洲SLE患者。在有和没有11个临床特征的患者之间比较了26个SLE相关SNP的基因型：10个美国流变学学会（ACR）分类标准（ANA除外）和疾病发作年龄。这些分析根据招募中心、顶级祖先信息标记、性别和随访时间进行了调整。排除与先前研究的样本重叠，以评估重复性。有三个新的关联：XKR 6和FAM 167 A-BLK中的SNP与狼疮性肾炎相关（OR分别为0.76和1.30，Pcorr分别为0.007和0.03），X染色体上的MECP 2的SNP与男性发病年龄较早相关。 先前报道的STAT 4与早期疾病发病年龄的相关性得到了证实。其他一些结果提示存在其他关联。总之，相关信号提供了支持一些以前的研究结果和表征狼疮肾炎，自身抗体和发病年龄的临床特征与SLE基因座更相关。一些SLE基因座除了增加对SLE的易感性之外还形成疾病表型。这种影响对于某些临床特征比对于其他临床特征更突出。然而，研究之间的结果仅部分一致，并且需要亚表型特异性GWAS来解开其遗传组分。
Systemic Lupus Erythematosus (SLE) shows a spectrum of clinical manifestations that complicate its diagnosis, treatment and research. This variability is likely related with environmental exposures and genetic factors among which known SLE susceptibility loci are prime candidates. The first published analyses seem to indicate that this is the case for some of them, but results are still inconclusive and we aimed to further explore this question. European SLE patients, 1444, recruited at 17 centres from 10 countries were analyzed. Genotypes for 26 SLE associated SNPs were compared between patients with and without each of 11 clinical features: ten of the American College of Rheumatology (ACR) classification criteria (except ANAs) and age of disease onset. These analyses were adjusted for centre of recruitment, top ancestry informative markers, gender and time of follow-up. Overlap of samples with previous studies was excluded for assessing replication. There were three new associations: the SNPs in XKR6 and in FAM167A-BLK were associated with lupus nephritis (OR = 0.76 and 1.30, Pcorr = 0.007 and 0.03, respectively) and the SNP of MECP2, which is in chromosome X, with earlier age of disease onset in men. The previously reported association of STAT4 with early age of disease onset was replicated. Some other results were suggestive of the presence of additional associations. Together, the association signals provided support to some previous findings and to the characterization of lupus nephritis, autoantibodies and age of disease onset as the clinical features more associated with SLE loci. Some of the SLE loci shape the disease phenotype in addition to increase susceptibility to SLE. This influence is more prominent for some clinical features than for others. However, results are only partially consistent between studies and subphenotype specific GWAS are needed to unravel their genetic component.
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影响因子：
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作者：
Moser, K. L.;Kelly, J. A.;Lessard, C. J.;Harley, J. B.
通讯作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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通讯作者：
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