Meta-analysis of HLA-DRB1 and HLA-DQB1 polymorphisms in Latin American patients with systemic lupus erythematosus.
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 DRbeta 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.
Castaño-Rodríguez
Natalia
N
Cellular Biology and Immunogenetics Unit, Corporación para Investigaciones Biológicas, Medellín, Colombia.
Diaz-Gallo
Lina-Marcela
LM
Pineda-Tamayo
Ricardo
R
Rojas-Villarraga
Adriana
A
Anaya
Juan-Manuel
JM
D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D007843:Latin America / Q000453:epidemiology; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen