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Theses

Évaluation du terrain génétique des hypersensibilités

Abstract : The physiopathology of drug hypersensitivity (HS) are only partially known. A genetic background for such drug allergy is still demonstrated but only few genes are identified. Using a candidate gene approach, we tested the association of NOD1 and 2 genes with betalactam HS and the association of several cytokines genes with some drug HS. Using a whole genome approach, we tried to discover new candidate gene for DRESS. Among 368 italian cases and controls and 387 spanish cases and 326 controls, we identified one polymorphism of NOD2 gene associated with a protective effect for italians and another polymorphism associated with higher risk of druh HS for spanians. No association with NOD1 polymorphims was identified. Among 118 cases and 236 controls, we noticed that IL1 polymorphisms (IL1-RN-A2 and IL1-? -511) and IL10 polymorphism (-592A) were associated with DRESS. Ending, among 18 DRESS, a whole-genome array let us identify variations containing KLRC2 and CESP1 genes. These studies demonstrate the implication of several genes involved in inflammation, antivirus response or drug metabolism in different drug HS. Fonctionnal studies are needed to confirm these results
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Anne-Claire Bursztejn. Évaluation du terrain génétique des hypersensibilités. Médecine humaine et pathologie. Université de Lorraine, 2013. Français. ⟨NNT : 2013LORR0344⟩. ⟨tel-01751220⟩

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