Background:Systemic lupus erythematosus (SLE)is an autoimmune disease under genetic control.Growing evidences support the genetic predisposition ofHLA-DRB1 gene polymorphisms to SLE,yet the results are not often repro...Background:Systemic lupus erythematosus (SLE)is an autoimmune disease under genetic control.Growing evidences support the genetic predisposition ofHLA-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 ofHLA-DRB1 gene (HLA-DR3and 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 23studies were retained for analysis,including 5261cases and 9838controls.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 =0.129and OR:1.68,95%CI:1.334-2.112,P =0.001,respectively).Subgroup analyses demonstrated that for both HLA-DR3and HLA-DR15polymorphisms,ethnicity was a possible source of heterogeneity.Specifically,HLA-DR3polymorphism was not associated with SLE in White populations (OR:1.60,95%CI:1.320-1.960,P =0.522)and HLA-DR15polymorphism 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-DR3and HLA-DR15polymorphisms,with observable significance for HLA-DR3in only population-based studies (OR:1.65,95% CI:1.370-1.990,P =0.244)and for HLA-DR15in both population-based and hospital-based studies (OR:1.38,95%CI:1.078-1.760, P =0.123and 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.展开更多
基金grants from the National Key Basic Research Program of China (No.2014CB541901) the National Nature Science Foundation of China (No.81573033) the National Key Research Program of China (No.2016YFC0906102).
文摘Background:Systemic lupus erythematosus (SLE)is an autoimmune disease under genetic control.Growing evidences support the genetic predisposition ofHLA-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 ofHLA-DRB1 gene (HLA-DR3and 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 23studies were retained for analysis,including 5261cases and 9838controls.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 =0.129and OR:1.68,95%CI:1.334-2.112,P =0.001,respectively).Subgroup analyses demonstrated that for both HLA-DR3and HLA-DR15polymorphisms,ethnicity was a possible source of heterogeneity.Specifically,HLA-DR3polymorphism was not associated with SLE in White populations (OR:1.60,95%CI:1.320-1.960,P =0.522)and HLA-DR15polymorphism 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-DR3and HLA-DR15polymorphisms,with observable significance for HLA-DR3in only population-based studies (OR:1.65,95% CI:1.370-1.990,P =0.244)and for HLA-DR15in both population-based and hospital-based studies (OR:1.38,95%CI:1.078-1.760, P =0.123and 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.
