Analysis of mutations and polymorphisms of genes in associates one liberation road bradykinin in patients with hereditary Angioedema

• Grant number: 15/25079-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2016
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Bosco Pesquero
• Grantee: Bruna Franca de Azevedo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Hereditary angioedema (HAE) is characterized by sudden episodes of edema that cause pain and discomfort that affect mainly upper and lower extremities, gastrointestinal tract, genitalia and face and can lead to death by suffocation when they reach the upper respiratory tract. In some patients, the severity and frequency of symptoms seem to be related to hormonal changes, specifically to estrogen levels. The HAE is a resulting autosomal dominant disorder mutation in the C1 inhibitor gene (C1INH) or specific mutations in factor XII gene coagulation (FXII), leading to an imbalance in via the liberation of bradykinin (BK), responsible for edema. Trauma, stress, and estrogen use may trigger seizures. Angioedema episodes may last for 1 to 5 days; the frequency of seizures varies from patient to patient as well as the location of edemas, of the same family bearing the same mutation. Several studies have been trying to understand the cause of the variation in severity of symptoms in HAE, however, the factors that lead to such diversity remain unknown. The objective of this project is to study the relationship of certain mutations and polymorphisms found in genes associated with the route of BK release in patients with HAE, analyzing their genetic and functional changes and correlated with the variation of symptoms of each patient. Classic polymorphisms are analyzed as new mutations found in earlier designs of our DNA chain. The HAE carriers selected patients will be amplified by PCR, the product analyzed by electrophoresis on an agarose gel and sequenced by the Sanger method. The identify the possible relationship of these changes in patients with HAE assist in understanding of their possible role in the modulation of crises.