Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?
Is FCGR2A a susceptibility gene to systemic lupus erythematosus in Chinese?
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DOI：
10.1177/0961203311409269
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发表时间：
2011-07
期刊：
影响因子：
2.6
通讯作者：
X. Zhou;Ji-Cheng Lv;LX Qin;HZ Yang;Feng Yu;M. Zhao;H. Zhang
中科院分区：
文献类型：
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作者：
X. Zhou;Ji-Cheng Lv;LX Qin;HZ Yang;Feng Yu;M. Zhao;H. Zhang
最近的全基因组关联扫描和复制研究加强了FCGR 2A是白种人系统性红斑狼疮（SLE）的易感基因。然而，以前的病例对照研究否定了中国人的这一结论。除了不同种族间的遗传异质性外，拷贝数变异（CNV）、非同质表型和把握度不足也可能是混杂因素。我们对1066名中国人（589名SLE患者和477名健康对照）进行了病例对照研究，并对2328名SLE患者和2313名健康对照进行了荟萃分析。通过TaqMan测定法检测FCGR 2A CNV和FCGR 2A 131 H/R [rs 1801274]。中国人FCGR 2A基因拷贝数无变异。进一步的病例对照研究表明FCGR 2A 131 H/R具有剂量-反应特征，并影响疾病的活动性、严重程度和预后。Meta分析结果显示FCGR 2A是中国人SLE的易感基因，优势比为1.094，人群归因危险度为0.031。通过综合策略，我们验证了FCGR 2A不具有群体特异性CNV。FCGR 2A 131 H/R与中国人SLE易感性有关，并影响疾病的活动性、严重程度和预后。中国人未检测到的关联来自于能力不足，而不是由于CNV或群体特异性遗传效应而造成的任何方法学障碍。
Recent genome-wide association scans and replication studies reinforce that FCGR2A is a susceptibility gene in systemic lupus erythematosus (SLE) in Caucasians. However, previous case control studies denied such conclusions in Chinese people. Besides genetic heterogeneity among different ethnicities, copy number variation (CNV), non-homogenous phenotypes and insufficient power may be confounders. We performed a case control study with 1066 Chinese (589 SLE patients and 477 healthy controls) and a meta-analysis based on 2328 SLE patients and 2313 healthy controls. FCGR2A CNV and FCGR2A131H/R [rs1801274] were detected by TaqMan assays. No variation of copy numbers of FCGR2A gene was found in Chinese. A further case control study suggested a dose–response character for FCGR2A131H/R and it affected disease activity, severity and prognosis. Finally, meta-analysis indicated FCGR2A that was a susceptibility gene to SLE in Chinese with an odds ratio of 1.094 and population attributable risk proportion of (PARP) 0.031. By an integrative strategy, we validate that FCGR2A bears no population-specific CNV. FCGR2A131H/R contributes to SLE susceptibility in Chinese, and affects disease activity, severity and prognosis. The undetected association in Chinese derives from under-power rather than any methodological obstacle due to CNV or population-specific genetic effect.