Author(s): Ferreira, Paula Sousa Alves, 1983-
Date: 2015
Persistent ID: http://hdl.handle.net/10451/18263
Origin: Repositório da Universidade de Lisboa
Subject(s): Farmacogenética; Nutrigenómica; Doença de Crohn; Enteropatias inflamatórias; Teses de doutoramento - 2015
Tese de doutoramento, Biologia (Genética), Universidade de Lisboa, Faculdade de Ciências, 2015
Crohn’s disease, a pathology of unknown origin, is characterized by a chronic inflammatory response that involves the entire gastrointestinal tract, a high heterogeneity in phenotype and a strong genetic component. It’s a disease with a greater incidence in industrialized countries, what suggests the importance of environmental factors in its pathogenesis, where diet patterns have been pointed out as possible cause. The treatment of this disease is very complex due to the severity of the clinical parameters and the variety of response to the existing therapies. This emphasizes the importance of the conjugation with genetic factors such as polymorphisms in key genes presented in inflammatory pathways, apoptosis, autophagy and metabolism and drug transportation. The main existing challenge results from the difficulty in predicting the disease development along the years, which turns the choice of appropriate therapeutic and control of symptoms problematic. With the purpose of answering to these questions, we have developed several studies, here compiled in this dissertation, that have the main goal of identifying clinical and genetic predictors of response to the normally used therapies that allowed the physicians to stratified their patients in order to apply a more personalized therapeutic based on individuals genetic profile. As main results emerges the identification of genetic polymorphisms in cytokine genes such as TNFα, LTα, IL1 e IL6 as associated with disease aggressiveness and development. The high consumption of glicids, lipids, saturated, monounsaturated and polyunsaturated fats appears as risk factors to greater disease aggressiveness. Clinical predictors such as patient’s age, surgery and perianal involvement and genetic predictors like Casp9 and MDR1 gene polymorphisms were associated with response to therapy. The future for the treatment of Crohn’s disease resides in the investment in pharmacogenetics and nutrigenetics studies, such as the studies described here, since they emerge as a benefit to the routinely clinical practice that contributes to a therapeutic and nutritional therapy personalized to each patient and, therefore, a better quality of life.
Fundação para a Ciência e a Tecnologia (FCT), SFRH/BD/64172/2009; Grupo de Estudos da Doença Inflamatória Intestinal (2009-2012)
