Study of the role of the gene promoter of the factor XII in hereditary angioedema

Abstract

The hereditary angioedema (HAE) is characterized by sudden episodes of painful edemas and discomfort which affects mainly the upper and lower extremities, gastrointestinal tract, genitals and face, and it can lead to death by asphyxiation in swelling of upper respiratory tract. In some patients, the gravity and frequency of the symptoms seems to be related to hormonal alteration, specifically to estrogen's levels. The HAE is an autosomal-dominant disorder resulting from mutations in the C1 inhibitor (C1-INH) or changes in the gene of the factor XII of coagulation (FXII), resulting in an unbalance in the pathway of bradykinin release, responsible for the edemas. The aim of this project is to study the promotor of FXII in patients with HAE who present a marked influence of estrogens in the clinical gravity, since this region has sequences of estrogen responsive element (ERE).The promoter region of the FXII gene from patients with HAE will be amplified by PCR and sequenced by the Sanger's method. The mutations found will be correlated with the influence of estrogen (use of contraceptive pills, menstrual periods, gestation, hormonal replacement) in the variation of gravity in the HAE episodes (frequency and duration of the episodes). The identification of mutations related to the influence of estrogen in the variation of the HAE symptoms will provide markers of this relation, assisting in the indication of a hormonal therapy in patients with HAE and avoiding the aggravation of the episodes. (AU)