Deletion of LCE3C and LCE3B Is a Susceptibility Factor for Psoriatic Arthritis: A Study in Spanish and Italian Populations and Meta-Analysis
Deletion of LCE3C and LCE3B Is a Susceptibility Factor for Psoriatic Arthritis: A Study in Spanish and Italian Populations and Meta-Analysis
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DOI：
10.1002/art.30340
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发表时间：
2011-07-01
影响因子：
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通讯作者：
Estivill, Xavier
中科院分区：
文献类型：
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作者：
Docampo, Elisa;Giardina, Emiliano;Estivill, Xavier
目标。LCE3C_LCE3B-del变异与银屑病和类风湿性关节炎有关。然而，它在银屑病关节炎(PSA)中的作用尚不清楚，最近的3项研究显示出相互矛盾的结果。为了研究LCE3C_LCE3B-del是否构成PSA易感性的危险因素，我们首先在来自西班牙和意大利人群的PSA患者中检测了LCE3CLCE3B-del，然后进行了包括先前病例对照研究的荟萃分析。我们在424名意大利PSA患者和450名未受影响的对照组的原始发现队列中，对LCE3C_LCE3B-del及其标签单核苷酸多态(SNP)rs4112788进行了基因分型。由225名PSA患者和469名对照受试者组成的西班牙复制队列也进行了基因分型。对7,758名对照受试者和2,325名PSA患者进行了荟萃分析。在意大利和西班牙的队列中，我们观察到PSA与LCE3CLCE3B-del tag SNP之间存在显著的相关性，总体校正P值为0.00019，相应的优势比为1.35(95%可信区间为1.14-1.59)。根据亚型进行的分层分析表明，与少关节疾病患者有更强的相关性。Meta分析证实PSA与LCE3C_LCE3B-del tag SNP.之间存在关联。LCE3CLCE3B-del是PSA的易感因子，证实在自身免疫性疾病中存在涉及表皮皮肤屏障的共同危险因子。
Objective. The LCE3C_LCE3B-del variant is associated with psoriasis and rheumatoid arthritis. Its role in psoriatic arthritis (PsA) is unclear, however, as shown by 3 recent studies with contradictory results. In order to investigate whether LCE3C_LCE3B-del constitutes a risk factor for PsA susceptibility, we first tested this variant in patients with PsA from Spanish and Italian populations and then performed a meta-analysis including the previous case-control studies.Methods. We genotyped LCE3C_LCE3B-del and its tag single-nucleotide polymorphism (SNP), rs4112788, in an original discovery cohort of 424 Italian patients with PsA and 450 unaffected control subjects. A Spanish replication cohort consisting of 225 patients with PsA and 469 control subjects was also genotyped. A meta-analysis considering 7,758 control subjects and 2,325 patients with PsA was also performed.Results. We observed a significant association between PsA and the LCE3C_LCE3B-del tag SNP in the Italian and Spanish cohorts, with an overall corrected P value of 0.00019 and a corresponding odds ratio of 1.35 (95% confidence interval 1.14-1.59). Stratified analyses by subphenotype indicated a stronger association for patients with oligoarticular disease. Meta-analysis including data from all previous published studies confirmed an association of PsA with the LCE3C_LCE3B-del tag SNP.Conclusion. LCE3C_LCE3B-del is a susceptibility factor for PsA, confirming the existence of a shared risk factor involving the epidermal skin barrier in autoimmune disorders.