|Tipo di tesi||Tesi di dottorato di ricerca|
|Titolo||Ruolo dei polimorfismi genetici nella diagnosi dei noduli tiroidei e della fisiopatologia gonadica|
|Titolo in inglese||The role of polymorphic gene variants in the diagnosis of thyroid nodules and gonadal pathophysiology|
|Settore scientifico disciplinare||MED/13 - ENDOCRINOLOGIA|
|Corso di studi||CLINICAL AND EXPERIMENTAL MEDICINE (CEM) - MEDICINA CLINICA E SPERIMENTALE|
|Data inizio appello||2017-03-27|
|Disponibilità||Accessibile via web (tutti i file della tesi sono accessibili)|
Introduzione. L’endocrinologia rappresenta una disciplina fertile per lo sviluppo di studi traslazionali nell’era post-genomica. La biologia molecolare ha un ruolo nel migliorare le conoscenze sulle dinamiche fisiopatologiche degli assi ormonali e per la diagnosi del cancro.
Background. Endocrinology has been a fertile ground for the development of translational studies in the post-genomic era. Molecular biology has a role in improving physiopathological knowledge of hormonal axes and to detect cancer. Aim. To study the role of genetics in thyroid cancer prediction risk and diagnosis. And to infer from genetic analysis the evolutionary and pathophysiological hypotheses of ovarian and thyroid diseases. Methods. Considering hypothalamo-pituitary-thyroid axis, the role of TRHR gene in regulating central sensitivity to levothyroxine has been investigated. Then, BRAF V600E mutation was detected and analyzed in thyroid fine needle aspiration biopsy (FNAB) washing liquid. A study about polycystic ovary syndrome (PCOS) phenotype-genotype relationship was performed considering single nucleotide polymorphisms. The same in silico approach was applied to thyroid cancer. Results. We demonstrated an association between hypothalamo-pituitary sensitivity and discrete alleles of TRHR in thyroidectomized patients under levothyroxine therapy. High-resolution melting proved to be a sensitive, cost-effective, time-saving technique for BRAF V600E detection in thyroid FNAB washing liquid. The in silico study of PCOS representative genes demonstrated some phenotype-genotype correlations. The phenotypic differences result from genetic drift due to a serial founder effect occurred during ancient human migrations. Finally, we demonstrated that it is possible to define peculiar genotypes predisposing to thyroid cancer, together with risk factors such as obesity and iodine exposure. Conclusions. All the mentioned results were published in international scientific journal, giving a contribution to the growing field of genetics in physiopathology and diagnosis of endocrinological diseases.