Childhood type 1 diabetes mellitus and risk factor of interactions between dietary cow's milk intake and HLA-DR3/DR4 genotype.

Short-term breastfeeding and early exposure to dairy products into infant diets, may be critical factors for development of type 1 diabetes. In this study, we investigate whether cow's milk proteins are risk factors for type 1 diabetes in genetically susceptible individuals (HLA DR3/DR4) by using statistical analysis and in silico approach. In order to verify the potential risk of the early introduction of cow's milk, we conducted this study to validate the veracity of this hypothesis in our population. We included 121 subjects, 55 type 1 diabetics and 74 controls from the region of Tlemcen (Algeria). Thus, the in silico approach was performed to determine the molecular mimicry region between Bovine serum albumin and beta-lactoglobulin with self-Islet antigen 2 and glutamate decarboxylase 65 by determining their sequences and their 3D structures. The risk factors associated with type 1 diabetes in a genetically predisposed individual (HLA DR3/DR4) retained by the logistic model are: type 1 and type 2 diabetes inheritance, the early introduction of cow's milk before 6 months and breastfeeding less than 9 months. Besides, the epitopes of cow's milk proteins have the capacity to bind to predisposing HLA class II molecules (HLA DR3/DR4) and induce an immune reaction by the secretion of Interleukin 4 (Th2) and Interferon (Th1) which lead to the destruction of pancreatic beta cells. The early introduction of cow's milk proteins in susceptible individuals is considered as risk factors for the pathogenesis of T1DM. The in silico approach confirm that BSA and BLG share sequence and structure homology with IA2 and GAD65.Communicated by Ramaswamy H. Sarma.