Gorodezky C, Olivo A, Alaez C, Vázquez M N, de la Rosa G, Debaz H, Robles C, Altamirano N, Layrisse Z, Balducci P L, Domínguez E, Herrera F, Montagnani S, Esparza B, Balbas O, Gunczler P, Lanes R, Amaro R, Zaro R, Fuenmayor V, Montoya F, Bedoya C I, Restrepo M C, Villegas A, Vicario J L
Departamento de Inmunogenética, INDRE, SSA, MEXICO D.F. cgorodeaUmailer.main.conacyt.mx
Gac Med Mex. 1997;133 Suppl 1:125-32.
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.
1型糖尿病是一种自身免疫性多基因疾病，其中MHC - II类基因对该疾病的贡献率为48%。本研究的目的是通过对3个拉丁美洲混血人群的免疫遗传学分析，为理解这些基因的分子关联提供指导。我们纳入了606名个体，其中349名1型糖尿病患者和257名健康对照，他们来自3个地理区域：墨西哥的墨西哥城、委内瑞拉的加拉加斯和哥伦比亚的麦德林。结果清楚地表明，在混血人群中，致糖尿病单倍型来自地中海血统，而保护性则归因于美洲印第安基因。结果表明，1型糖尿病表达的相关序列位于DRB1和DQB1基因座，DQA1残基的贡献最小。决定肽识别和介导细胞自身免疫反应的TH1细胞诱导的序列位于DRB1的57和74位（分别为天冬氨酸和谷氨酸，具有保护作用），受DQβ链中57位天冬氨酸的调节。这些数据表明，DRB1 - DQB1单倍型对1型糖尿病的表达至关重要，并为疾病管理开辟了新途径。
