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

Abstract

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

Keywords:

• Type 1 diabetes
• HLA DR3/DR4
• cow’s milk proteins
• self-antigens
• molecular mimicry

Acknowledgement

We wish to thank the co-authors for their collaboration.

Conflict of interest

Have not a direct or indirect interest (financial or nature) with a private, industrial or commercial organization relationship with the presented subject.

Ethical approval

People's Democratic Republic of Algeria Ministry of Higher Education and Scientific Research University Aboubekr Belkaïd, Tlemcen Faculty of Sciences of Nature and Life and Science of the Earth and the Universe

Authorization of the ethics committee

Within the framework of a doctoral training, domiciled within of the Faculty of Sciences of Nature and Life and Science of the Earth and the Universe, University of Tlemcen the department of Biology.

Majda Dali-Sahi and the Nouria Dennouni-Medjati, respectively, responsible and member of the Doctoral Training ‘Molecular Biology’; have jointly filed with the council of ethics and professional conduct University of Tlemcen; A project of research entitled ‘Modulating effects of heredity and environmental risk factors on diabetes (type 1 and type 2) in populations of the far west of Algeria’. And to have his agreement concerning the ethics aspect and deontological of the project and to recommend this last to the concerned services of University Hospital Center of Tlemcen. Having inquired of the two project managers regarding compliance with the rules of ethics and professional conduct which will govern the various stages of carrying out this research, the members of CEDUT, also convinced of the scientific interest of such a study, have obtained the necessary clarifications as to the meeting of the ethical and deontological conditions in the respect of which the data collection and the confidentiality of the results will be carried out.

Councils’ member authorize the persons concerned, as well as all of their doctoral students, to carry out their research work and request the services concerned of the University Hospital Center of Tlemcen to provide their assistance in the proper realization of this work.

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People's Democratic Republic of Algeria

Ministry of Higher Education and Scientific Research

University of Tlemcen

Department of Biology

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Additional information

Funding

The authors received no financial support for the research, authorship and/or publication of this article.