1. [High- and low-risk molecular sequences in autoimmune diseases. An analysis of type I diabetes in Latin America].
- Author
-
Gorodezky C, Olivo A, Alaez C, Vázquez MN, de la Rosa G, Debaz H, Robles C, Altamirano N, Layrisse Z, Balducci PL, Domínguez E, Herrera F, Montagnani S, Esparza B, Balbas O, Gunczler P, Lanes R, Amaro R, Zaro R, Fuenmayor V, Montoya F, Bedoya CI, Restrepo MC, Villegas A, and Vicario JL
- Subjects
- Adolescent, Adult, Age of Onset, Asia ethnology, Autoimmune Diseases ethnology, Autoimmune Diseases genetics, Child, Child, Preschool, Colombia epidemiology, Diabetes Mellitus, Type 1 ethnology, Diabetes Mellitus, Type 1 genetics, Disease Susceptibility, Ethnicity genetics, Europe ethnology, Female, Genotype, HLA-DQ Antigens genetics, HLA-DQ alpha-Chains, HLA-DQ beta-Chains, HLA-DR Antigens genetics, HLA-DRB1 Chains, Haplotypes, Humans, Indians, North American, Indians, South American, Infant, Latin America epidemiology, Male, Mexico epidemiology, Risk Factors, Venezuela epidemiology, White People, Autoimmune Diseases epidemiology, Diabetes Mellitus, Type 1 epidemiology, Genes, MHC Class II
- Abstract
Type I diabetes is an autoimmune and a polygenic disease, in which MHC-class II genes contribute to 48% of the disease. The aim of the present study, is to provide a guideline to understanding the molecular association of these genes, through the immunogenetic analysis of 3 Latin american mestizo populations. We included 606 individuals, 349 patients with DMDI and 257 healthy controls coming from 3 geographical areas: Mexico City, Mexico; Caracas, Venezuela and Medellin, Colombia. The results clearly indicate that in mestizo groups, the diabetogenic haplotypes are from mediterranean ancestry, while protection is due to Amerindian genes. It was demonstrated that the relevant sequences for IDDM expression are located to DRB1 and DQB1 loci with a minimal contribution of DQA1 residues. The sequences determining peptide recognition and the induction of TH1 cells mediating the cellular autoimmune response are in positions DRB1-57 and 74 (an aspartic acid and a glutamic acid respectively, confer protection), modulated by D-57 in the DQ, 8 chain. These data show that DRB1-DQB1 haplotypes are central for IDDM expression and open new pathways for the disease management.
- Published
- 1997