HLA-Class II in Latin American patients with type 1 diabetes.
OBJECTIVE
To identify and estimate the common effect size of HLA-Class II contributing to susceptibility on T1D in Latin America (LA) through a meta-analysis.


METHODS
A systematic review of the literature searching for all HLA-Class II alleles and susceptibility for T1D case-control studies performed in LA was made up to October 2009. Effect summary ORs and 95% CI were obtained by means of the random effect model. A prediction model that identifies peptides binding to HLA-DR alleles that were significantly associated with T1D throughout the meta-analysis was done.


RESULTS
21 studies were included (1138 cases and 1920 controls). DRB1*0301 (OR: 9.65; 95% CI: 5.69-16.36; p<0.0001), DRB1*1201 (OR: 4.84; 95% CI: 1.97-11.91; p=0.001), DQB1*0302 (OR: 4.58; 95% CI: 3.36-6.26; p<0.0001), DQA1*0301(OR: 3.02; 95% CI: 1.37-6.65; p=0.0059) and DQB1*0602 (OR: 0.19; 95% CI: 0.11-0.33; p<0.0001), DRB1*14 (OR: 0.18; 95% CI: 0.06-0.55; p=0.0024), and DQB1*0501 (OR: 0.47; 95% CI: 0.26-0.83; p=0.0097) were the most significant alleles associated with T1D. DRB1*0301-DQA1*0501-DQB1*0201 (OR: 13.50; 95% CI: 3.85-47.28; p<0.0001) and DRB1*1301-DQB1*0603 (OR: 0.25; 95% CI: 0.1-0.65; p=0.004) were the most significant risk and protective haplotypes associated, respectively. There were peptides binding to significantly HLA-DRB1 alleles and haplotypes found through the meta-analysis from islet cell protein tyrosine phosphatase and glutamic acid decarboxylase.


CONCLUSIONS
These results strengthen the effect of HLA-Class II on T1D in LA similar to Caucasians regardless of the latitudinal gradient and admixture. The shared chemical characteristics in critical pockets could explain the predisposition to present a "diabetogenic peptide" to T cells in this population.
Rojas-Villarraga
Adriana
A
Center for Autoimmune Diseases Research, Universidad del Rosario, Bogotá, Colombia. adrirojas@gmail.com
Botello-Corzo
Diana
D
Anaya
Juan-Manuel
JM
D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics* / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D007843:Latin America; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000276:immunology* / Q000378:metabolism
D001324:Autoantigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D010446:Peptide Fragments; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase