Dissection of the FCGR3A association with RA: increased association in men and with autoantibody positive disease
Dissection of the FCGR3A association with RA: increased association in men and with autoantibody positive disease
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DOI：
10.1136/ard.2009.110874
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发表时间：
2009-08
影响因子：
27.4
通讯作者：
James I. Robinson;J. Barrett;John C. Taylor;Marc Naven;D. Corscadden;A. Barton;A. Wilson;P. Emery;J. Isaacs;A. Morgan
中科院分区：
文献类型：
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作者：
James I. Robinson;J. Barrett;John C. Taylor;Marc Naven;D. Corscadden;A. Barton;A. Wilson;P. Emery;J. Isaacs;A. Morgan
目的 由于节段重复的混杂效应，类风湿性关节炎 (RA) 的全基因组关联研究未能检查 FCGR 基因簇。本研究旨在复制之前的候选基因研究，这些研究已确定 FCGR3A-158V 等位基因与 RA 之间存在显着关联，然后试图估计特定的亚组效应。方法 FCGR3A-158F/V 基因分型在英国白种人复制队列中进行，该队列由 2049 名 RA 患者和 1156 名对照者组成。根据性别和自身抗体（类风湿因子 (RF) 和环瓜氨酸肽 (CCP)）状态对 2963 名 RA 患者和 1731 名对照人群进行亚组分析，评估关联程度。使用逻辑回归来测试 FCGR3A 和 HLA-DRB1 共享表位 (SE) 等位基因之间的相互作用。结果 在合并的 RA 队列中，发现 FCGR3A-158V 等位基因与纯合性存在边界关联（OR 1.2，p=0.05），在男性中更强（OR 1.7，p=0.01）。按自身抗体状态分层显示 RF 和 CCP 阳性 RA 的风险增加。 FCGR3A-158V 和 HLA-DRB1 SE 相互作用的分析揭示了这两个基因在自身抗体阳性 RA 易感性中的作用，但没有相互作用的证据。结论 FCGR3A 是发生自身抗体阳性 RA 的危险因素，特别是在男性中，有证据表明与 HLA-DRB1 SE 具有相乘效应。
Objectives Genome-wide association studies in rheumatoid arthritis (RA) have failed to examine the FCGR gene cluster because of the confounding effects of segmental duplication. This study aimed to replicate previous candidate gene studies that had identified a significant association between the FCGR3A-158V allele and RA and then sought to estimate specific subgroup effects. Methods FCGR3A-158F/V genotyping was undertaken in a UK Caucasian replication cohort comprising 2049 patients with RA and 1156 controls. Subgroup analyses assessing the magnitude of association according to gender and autoantibody (rheumatoid factor (RF) and cyclic citrullinated peptide (CCP)) status were undertaken in a pooled cohort of 2963 patients with RA and 1731 controls. Logistic regression was used to test for interaction between FCGR3A and HLA-DRB1 shared epitope (SE) alleles. Results In the combined RA cohort, borderline association with homozygosity was found for the FCGR3A-158V allele (OR 1.2, p=0.05), which was stronger in men (OR 1.7, p=0.01). Stratification by autoantibody status showed an increased risk in RF and CCP positive RA. Analysis of the FCGR3A-158V and HLA-DRB1 SE interaction revealed roles for both genes in susceptibility to autoantibody positive RA, with no evidence of interaction. Conclusions FCGR3A is a risk factor for the development of autoantibody positive RA, particularly in men, with evidence of a multiplicative effect with HLA-DRB1 SE.