Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: A large case-control study and meta-analysis
Chemokine receptor 5 (CCR5) delta 32 polymorphism in lupus nephritis: A large case-control study and meta-analysis
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DOI：
10.3109/08916934.2014.906581
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发表时间：
2014-09-01
期刊：
影响因子：
3.5
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Cheng, Fa-Juan;Zhou, Xu-Jie;Zhang, Hong
目的：最近的动物实验表明，CCR5缺陷狼疮小鼠（CCR5(-/-)）与狼疮肾炎加重密切相关。CCR5 Delta 32变异是CCR5的非同义突变，导致CCR5功能改变。然而，CCR5 δ 32突变在人类狼疮性肾炎中很少有文献报道。方法：进行了一项包括2010个中国人群样本的大型病例对照研究，随后进行了一项荟萃分析，结合当前和先前发表的研究，探讨CCR5 Delta 32对狼疮性肾炎易感性的影响。结果：仅在狼疮性肾炎患者中检测到4个CCR5 δ 32杂合子携带者。我们在研究人群中未检测到CCR5 Delta 32纯合子。在meta分析中，包括1092例病例和2229例对照，我们发现研究之间存在很大的异质性（p < 0.001, I-2 = 89.6%）。此外，分层和敏感性分析表明，种族和CCR5 Delta 32等位基因频率是异质性的主要来源。在没有明显异质性的亚组中，我们观察到CCR5 Delta 32与狼疮肾炎风险呈正相关（p < 0.05）。结论：我们的研究证实，CCR5 Delta 32突变在中国汉族人群中是一种非常罕见的变异。然而，CCR5 Delta 32可能在狼疮肾炎易感性中发挥作用。需要进一步的重复实验和功能研究。
Objectives: Recent animal experiments showed that CCR5-deficient lupus mice (CCR5(-/-)) were closely associated with aggravated lupus nephritis. CCR5 Delta 32 variation, a nonsynonymous mutation of CCR5, resulted in altered CCR5 function. However, the CCR5 Delta 32 mutation in human lupus nephritis has been rarely reported in the literature. Methods: A large case-control study that included 2010 samples from a Chinese population was conducted, followed by a meta-analysis combining the current and previously published studies to explore the effect of CCR5 Delta 32 on lupus nephritis susceptibility. Results: Four CCR5 Delta 32 heterozygote carriers were detected in lupus nephritis patients only. We detected no CCR5 Delta 32 homozygotes in our study population. In the meta-analysis, including 1,092 cases and 2,229 controls, we found great heterogeneity between studies (p < 0.001, I-2 = 89.6%). Furthermore, stratified and sensitivity analyses suggested that ethnicity and CCR5 Delta 32 allele frequency were the main origin of heterogeneity. In the subgroups without obvious heterogeneity, we observed a positive correlation between CCR5 Delta 32 and lupus nephritis risk (p < 0.05). Conclusions: Our study confirmed that the CCR5 Delta 32 mutation is a very rare variation found in the Chinese population with Han ethnicity. However, CCR5 Delta 32 might play a role in lupus nephritis susceptibility. Future replications and functional studies are needed.