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Master Thesis

Impact des facteurs génétiques et environnementaux sur le déclenchement du diabète de type 1

Abstract : Type 1 diabetes (T1DM) is a chronic disease characterized by progressive destruction of the β cells of the islets of the pancreas. The incidence of T1DM is constantly increasing worldwide (3% per year), with a growing increase in toddlers (less than 5 years old at diagnosis). This increasingly early onset, linked on the one hand to genetic factors, and on the other hand to environmental factors, suggests that the latter, which are currently not well identified, have evolved to have a greater impact on the onset of insulin-dependent diabetes. The identification of Major Histocompatibility Complex (MHC) markers of genetic predisposition to the development of T1DM has been a major advance in the understanding of this complex disease. However, not everyone who has the genetic markers for predisposition will develop the disease. Based on this assumption, environmental factors serving as "triggers" of the autoimmune process have been suggested. The objective of this work is to determine the genetic factors involved in the triggering of T1DM on the one hand and to take stock of the numerous environmental hypotheses on the other hand. Screening of the human genome has identified eighteen different genomic regions involved in the predisposition to T1DM, labelled from IDDM1 to IDDM18. IDDM1, the MHC gene locus, IDDM2, the INS insulin gene locus, and IDDM 12, the CTLA4 gene locus, are the main candidates for the development of T1DM. The analysis of the different IDDMs suggests that the susceptibility of diabetes is related to the joint effect of different MHC genes and other non-MHC genes with action at the thymus level or directly at the β-cell level. At the environmental level, the joint effect of several factors also seems to be at the origin of the triggering of T1DM. Among them, an infection by certain viruses, particularly the Coxsackie virus, seems to be a serious hypothesis given the evidence found in the literature. The hygienic hypothesis states that a decrease in the number of infections and infestations during early childhood and a less diverse symbiotic intestinal flora lead the immune system towards autoimmunity. This is the hypothesis that would partly explain the reason for the increased incidence in toddlers. Determining the exact impact of environmental factors influencing the risk of type 1 diabetes and a better understanding of the mechanisms involved remains paramount in the potential implications for prevention.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03496626
Contributor : Jean-Hugues Morneau Connect in order to contact the contributor
Submitted on : Monday, December 20, 2021 - 2:47:33 PM
Last modification on : Tuesday, December 21, 2021 - 3:47:21 AM

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  • HAL Id : dumas-03496626, version 1

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Lyes Bouzouagh. Impact des facteurs génétiques et environnementaux sur le déclenchement du diabète de type 1. Sciences pharmaceutiques. 2021. ⟨dumas-03496626⟩

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