Abstract
BackgroundHereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema–formation, which may occur in response to stress. The individual’s response to stress stimuli is partly genetically determined. Activation of the hypothalamic–pituitary–adrenal axis results in the release of cortisol. In turn, the secreted gluco- and mineralocorticoids affect the metabolism, as well as the cardiovascular and immune systems. We hypothesized that changes in serum cortisol level and polymorphisms of the glucocorticoid receptor (GR) modify the individual sensitivity to stressor stimuli of C1-INH-HAE patients.ResultsWe compared the response to stress with Rahe’s Brief Stress and Coping Inventory of 43 C1-INH-HAE patients, 18 angioedema patients and 13 healthy controls. 139 C1-INH-HAE patients and 160 healthy controls were genotyped for glucocorticoid receptor polymorphisms BclI, N363S and A3669G. Serum cortisol levels were determined during attacks and during symptom-free periods in 36 C1-INH-HAE patients. The relationships between clinical, laboratory data and GR SNPs (Single Nucleotide Polymorphisms) were assessed using ANOVA. C1-INH-HAE patients have decreased coping capabilities compared to healthy controls. Cortisol levels were significantly higher during attacks than in symptom-free periods (p = 0.004). The magnitude of the elevation of cortisol levels did not show a significant correlation with any clinical or laboratory data. Among the C1-INH-HAE patients, the carriers of the A3669G allele had significantly lower cortisol levels, and increased body mass index compared with non-carriers.ConclusionsThe higher cortisol level observed during attacks may reflect the effect of a stressful situation (such as of the attack itself), on the patients’ neuroendocrine system. In A3669G carriers, the lower cortisol levels might reflect altered feedback to the hypothalamic–pituitary–adrenal axis, due to decreased sensitivity to glucocorticoids.
Highlights
Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder
We investigated whether the clinical manifestations of C1-INH-HAE may be different in carriers of the three single nucleotide polymorphisms (SNP) of the glucocorticoid receptor (GR) gene because these SNPs have been associated with altered GC sensitivity
The evaluation of response to stress We did not find significant differences among the stress responses as measured with the Rahe’s Brief Stress and Coping Inventory tests in patients diagnosed with C1INH-HAE, in angioedematous patients, and healthy controls, using the Kruskal-Wallis one-way analysis of variance test (p = 0.1725)
Summary
Hereditary angioedema caused by C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder. C1-INH-HAE is characterized by edema–formation, which may occur in response to stress. Activation of the hypothalamic–pituitary–adrenal axis results in the release of cortisol. Hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE) is a rare, autosomal dominant disorder, which belongs to bradykinin-mediated angioedemas [1]. The deficiency of a serine protease protein C1-inhibitor (C1-INH) results in the activation of four plasma cascade systems (fibrinolytic, coagulation, kinin, and complement cascades), and this leads to the release of bradykinin from. Chronic stress as a general risk factor for the development of several diseases; it can modify disease activity [7,8,9,10]
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