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META ANALYSIS
Year : 2018  |  Volume : 131  |  Issue : 23  |  Page : 2844-2851

Association of HLA-DR3 and HLA-DR15 Polymorphisms with Risk of Systemic Lupus Erythematosus


1 Department of Dermatology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China
2 Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China

Correspondence Address:
Dr. Yong Cui
Department of Dermatology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0366-6999.246058

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Background: Systemic lupus erythematosus (SLE) is an autoimmune disease under genetic control. Growing evidences support the genetic predisposition of HLA-DRB1 gene polymorphisms to SLE, yet the results are not often reproducible. The purpose of this study was to assess the association of two polymorphisms of HLA-DRB1 gene (HLA-DR3 and HLA-DR15) with the risk of SLE via a comprehensive meta-analysis. Methods: This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Case-control studies on HLA-DRB1 and SLE were searched from PubMed, Elsevier Science, Springer Link, Medline, and Cochrane Library database as of June 2018. Analysis was based on the random-effects model using STATA software version 14.0. Results: A total of 23 studies were retained for analysis, including 5261 cases and 9838 controls. Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]: 1.60, 95% confidence interval (CI): 1.316–1.934, P = 0.129 and OR: 1.68, 95% CI: 1.334–2.112, P = 0.001, respectively). Subgroup analyses demonstrated that for both HLA-DR3 and HLA-DR15 polymorphisms, ethnicity was a possible source of heterogeneity. Specifically, HLA-DR3 polymorphism was not associated with SLE in White populations (OR: 1.60, 95% CI: 1.320–1.960, P = 0.522) and HLA-DR15 polymorphism in East Asian populations (OR: 1.65, 95% CI: 1.248–2.173, P = 0.001). In addition, source of control was another possible source for both HLA-DR3 and HLA-DR15 polymorphisms, with observable significance for HLA-DR3 in only population-based studies (OR: 1.65, 95% CI: 1.370–1.990, P = 0.244) and for HLA-DR15 in both population-based and hospital-based studies (OR: 1.38, 95% CI: 1.078–1.760, P = 0.123 and OR: 2.08, 95% CI: 1.738–2.490, P = 0.881, respectively). Conclusions: HLA-DRB1 gene may be a SLE-susceptibility gene, and it shows evident ethnic heterogeneity. Further prospective validations across multiple ethnical groups are warranted.

 

 Abstract in Chinese

系统性红斑狼疮HLA-DR3HLA-DR15基因多态性Meta分析

摘要

背景:系统性红斑狼疮是一种遗传性自身免疫疾病,研究发现其发病与HLA-DRB1基因遗传多态性相关。本研究旨在通过荟萃分析评估HLA-DRB1基因的两个基因多态性(HLA-DR3HLA-DR15)与SLE风险之间的关系。

方法:本研究符合PRISMA声明。从PubMed,Elsevier Science,Springer Link,Medline和Cochrane图书馆数据库中搜索了截至2018年6月对HLA-DRB1和SLE的病例对照研究。通过STATA14.0软件建立随机效应模型进行分析。

结果:本文共纳入23篇文献进行分析,包括5261例和9838例对照。总体分析显示,HLA-DR3HLA-DR15多态性与SLE的显着风险相关(优势比[OR]:1.595,95%置信区间(CI):1.316-1.934,P <0.01和OR:1.678,95 %CI:1.334-2.112,分别为P <0.001)。亚组分析表明, HLA-DR3HLA-DR15多态性,种族是异质性的可能来源。具体而言,HLA-DR3多态性与白人群体中的SLE显著相关(OR:1.60,95%CI:1.29-1.99,P <0.01),以及东亚人群中的HLA-DR15多态性(OR:1.646,95%CI: 1.248-2.173,P <0.01)。此外,患者来源是HLA-DR3HLA-DR15异质性的另一个可能来源,社区来源的人群分析研究中可发现HLA-DR3异质性有统计学意义(OR:1.65,95%CI:1.37-1.99,P <0.01)。在HLA-DR15社区/医院人群来源分析中,同样具有统计学意义(OR:1.378,95%CI:1.078-1.760,P <0.01和OR:2.08,95%CI:1.738-2.49,P <0.01)。

结论 HLA-DRB1基因可能是SLE易感基因,具有种族异质性。



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