Standardizing a methodology to sequence Factor XII, C1 inhibitor esterase (C1INH) and kinin B2 receptor genes. Analysis of the relationship between the mutations in these three genes with the symptoms of Hereditary Angioedema (HAE)

• Grant number: 11/15837-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: João Bosco Pesquero
• Grantee: Nathália Cagini
• Host Institution: Fundação de Apoio à Universidade Federal de São Paulo (FAP-UNIFESP). São Paulo , SP, Brazil

Abstract

The hereditary angioedema (HAE) is characterized by repetitives episodes of painful edemas, discomfort and according to their location can cause disfigurement of the individual. The edemas affect mainly the upper and lower extremities, gastrointestinal tract, genitals and face. If untreated, it can lead to death due to laryngeal edema. The HAE is an autosomal dominant disorder resulting from mutations in the C1 esterase inhibitor (HAE type 1 and 2) or the result of missense mutations in the factor XII, leading to an overproduction of bradykinin (HAE type 3). The aim of this project is to standardize the sequencing of the target genes of HAE (C1 esterase inhibitor, factor XII and kinin B2 receptor) and to investigate the relationship between the mutations in these genes with the response to the standard treatment currently used in the clinics. We will also evaluate the kallikrein activity in the peripheral blood of individuals with HAE. Thus, genomic DNA will be extracted from HAE patients from peripheral blood cells. The PCR will be performed with genomic DNA from patients with specifics oligos to the flanking regions of all exons and RNA followed by sequencing. Another aim of this project will also be to determine the relationship between new and already described mutations in the kinin B2 receptor to the response to the drug used in the clinics for the treatment of HAE, Fyrazyr (kinin B2 receptor antagonist - Icatibant or HOE145). The results of this project will help in the development of new HAE therapies and to determine patients with different responses to the standard treatment used in the clinics.