Glucocorticoid receptor gene polymorphisms in hereditary angioedema with C1-inhibitor deficiency

Zsuzsanna Zotter, Zsolt Nagy, Attila Patócs, Dorottya Csuka, Nóra Veszeli, Kinga Viktória Kohalmi, Henriette Farkas

Research output: Contribution to journalArticle

2 Citations (Scopus)


Background: 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. 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. Results: We 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. Conclusions: The 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.

Original languageEnglish
Article number5
JournalOrphanet journal of rare diseases
Issue number1
Publication statusPublished - Jan 10 2017


  • C1-inhibitor deficiency
  • Coping
  • Emotional stress
  • Glucocorticoid polymorphisms
  • Glucocorticoid sensitivity
  • Hereditary angioedema
  • Trigger factor

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

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