Meta-analysis of HLA-DRB1 and HLA-DQB1 polymorphisms in Latin American patients with systemic lupus erythematosu

Objective To estimate the common effect size of HLA-DRB1 and -DQB1 alleles on systemic lupus erythematosus (SLE) susceptibility across Latin America populations through a meta-analysis. Methods Case-control studies on HLA class II association with SLE in Latin America were searched up to August 2007. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained by means of the random effect model. Results Eleven studies were selected, which included 747 cases and 1180 controls. Associations with SLE susceptibility were found for HLA-DR2 (OR: 1.75; 95% CI: 1.40–2.19) and -DR3 (OR: 2.02; 95% CI: 1.44–2.83) groups. HLA-DRB1 0301 allele disclosed the strongest association (OR: 2.14; 95% CI: 1.28–3.56). HLA-DR3-DQ2 haplotype was a risk factor (OR: 2.92; 95% CI: 1.66–5.14). A protective effect was found for the HLA-DR5 group (OR: 0.43; 95% CI: 0.27–0.67), mainly due to a negative association between HLA-DRB1 1101 allele and disease (OR: 0.21; 95% CI: 0.06–0.72). Functional analysis of susceptibility and protective alleles revealed physicochemical differences of critical amino acids shaping the peptide-binding groove at DRβ chain allowing us to infer an approach to understand the role of HLA in SLE. No significant association was established for HLA-DQB1 alleles. Conclusions HLA-DRB1 gene is a mayor factor for development of SLE in Latin Americans.