Genetic determinants of C1 inhibitor deficiency angioedema age of onset

Panagiota Gianni, Gedeon Loules, Maria Zamanakou, Maria Kompoti, Dorottya Csuka, Fotis Psarros, Markus Magerl, Dimitru Moldovan, Marcus Maurer, Matthaios G. Speletas, Henriette Farkas, Anastasios E. Germenis

Research output: Article

9 Citations (Scopus)


Background: In view of the large heterogeneity in the clinical presentation of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), great efforts are being made towards detecting measurable biological determinants of disease severity that can help to improve the management of the disease. Considering the central role that plasma kallikrein plays in bradykinin production, we investigated the contribution of the functional polymorphism KLKB1 -428G/A to the disease phenotype. Methods: We studied 249 C1-INHHAE patients from 114 European families, and we explored possible associations of C1-INH-HAE clinical features with carriage of KLKB1 -428G/A, combined or not with that of the functional F12 -46C/T polymorphism. Results: Carriers of the G allele of the KLKB1 -428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [ p < 0.001], depending on the zygocity status), while carriers of both the KLKB1 -428G/A and the F12 -46C/T polymorphism displayed an 8.8-year delay in disease onset ( p < 0.001) and a 64% lower probability of needing long-Term prophylactic treatment ( p = 0.019). Conclusions: These findings support our initial hypothesis that functional alterations in genes of proteins involved in bradykinin metabolism and function affect the clinical phenotype and possibly contribute to the pathogenesis of C1-INH-HAE. Given that an earlier onset of symptoms is inversely correlated with the subsequent course of the disease and, eventually, the need for long-Term prophylaxis, these polymorphisms may be helpful prognostic biomarkers of disease severity.

Original languageEnglish
Pages (from-to)200-204
Number of pages5
JournalInternational archives of allergy and immunology
Issue number3-4
Publication statusPublished - jan. 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gianni, P., Loules, G., Zamanakou, M., Kompoti, M., Csuka, D., Psarros, F., Magerl, M., Moldovan, D., Maurer, M., Speletas, M. G., Farkas, H., & Germenis, A. E. (2017). Genetic determinants of C1 inhibitor deficiency angioedema age of onset. International archives of allergy and immunology, 174(3-4), 200-204.