title: Human leukocyte antigen class II and type 1 diabetes in Latin America: a combined meta-analysis of association and family-based studies.
abstract: Conclusions from association studies could be spurious because of population stratification; therefore we combined association with family studies seeking to confirm which human leukocyte antigen (HLA) class II alleles/haplotypes were associated with type 1 diabetes (T1D) in the admixed Latin America. By calculating the effect summary odds ratios (OR) and their 95% confidence intervals (95% CI), data up to June 2010 showed that risk associations were observed with DRB1*0301-DQA1*0501-DQB1*0201 (odds ratio [OR]: 7.51; 95% confidence interval [CI]: 3.69-15.25) and DQB1*0302 in presence of DRB1*0405 (OR: 11.64; 95% CI: 3.15-43.01) or DRB1*0401 (OR: 5.85; 95% CI: 3.07-11.14). In contrast, DRB1*0404-DQB1*0302 had a nonsignificant TID risk (OR: 2.23; 95% CI: 0.91-5.43). T1D protective associations were observed with DRB1*11-DQA1*0501-DQB1*0301 (OR: 0.24; 95% CI: 0.1-0.56) and DRB1*15-DQA1*0102-DQB1*0602 (OR: 0.35; 95% CI: 0.17-0.73). These results were similar to those observed in Caucasian and other populations, thus highlighting the primary role of class II HLA in T1D regardless of ethnicity. A DRB1*04 risk hierarchy was confirmed with the DRB1*0405 being in the top. A binding prediction analysis disclosed possible receptor-ligand interactions in the HLA-antigenic peptide complex.
authors.affiliation: Center for Autoimmune Diseases Research, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia. ricardo.cifuentesgarcia@gmail.com
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Cifuentes
authors.forename: Adriana
authors.initials: A
authors.lastname: Rojas-Villarraga
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D019295:Computational Biology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007843:Latin America; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology
chemical_list: D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D010455:Peptides