Association of HLA-DR1, HLA-DR13, and HLA-DR16 Polymorphisms with Systemic Lupus Erythematosus: A Meta-Analysis

Abstract

Objectives. The principal purpose of this meta-analysis was to assess the association between HLA-DRB1 (HLA-DR1, HLA-DR13, and HLA-DR16) polymorphisms and SLE susceptibility. Methods. We searched published case-control studies on the association between HLA-DRB1 polymorphisms and SLE susceptibility from PubMed and Web of Science databases. The pooled ORs with 95% CIs were utilized to estimate the strength of association of HLA-DR1, HLA-DR13, and HLA-DR16 polymorphisms and SLE susceptibility by fixed effect models. We also performed sensitivity analysis, trial sequential analysis, Begg’s test, and Egg’s test in this meta-analysis. Results. A total of 18 studies were included in this meta-analysis. Overall analysis showed that HLA-DR1 and HLA-DR13 polymorphisms were associated with a decreased risk of SLE ( $\text{OR}=0.76$ , 95% CI: 0.65-0.90, $P<0.01$ ; $\text{OR}=0.58$ , 95% CI: 0.50-0.68, $P<0.01$ ), and HLA-DR16 polymorphism was associated with an increased risk of SLE ( $\text{OR}=1.70$ , 95% CI: 1.24-2.33, $P<0.01$ ). In subgroup analysis of ethnicity, the results were as follows: HLA-DR1 polymorphism in Caucasians ( $\text{OR}=0.76$ , 95% CI: 0.58-0.98, $P=0.04$ ) and North Americans ( $\text{OR}=0.64$ , 95% CI: 0.42-0.96, $P=0.03$ ); HLA-DR13 polymorphism in Caucasians ( $\text{OR}=0.62$ , 95% CI: 0.47-0.82, $P<0.01$ ) and East Asians ( $\text{OR}=0.44$ , 95% CI: 0.34-0.57, $P<0.01$ ); and HLA-DR16 polymorphism in East Asians ( $\text{OR}=2.62$ , 95% CI: 1.71-4.03, $P<0.01$ ).Conclusions. This meta-analysis showed that HLA-DR1 and HLA-DR13 are protective factors for SLE, and HLA-DR16 is a risk factor. Due to the limitations of this meta-analysis, the association between HLA-DRB1 polymorphisms and SLE susceptibility needs to be further researched before definitive conclusions are proved.