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-INH-HAE 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.
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-INH-HAEpatients 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.
Authors: Fernando Corvillo; María Eugenia de la Morena-Barrio; Carmen Marcos-Bravo; Margarita López-Trascasa; Vicente Vicente; Jonas Emsley; Teresa Caballero; Javier Corral; Alberto López-Lera Journal: Front Genet Date: 2020-09-10 Impact factor: 4.599
Authors: Camila Lopes Veronez; Anne Aabom; Renan Paulo Martin; Rafael Filippelli-Silva; Rozana Fátima Gonçalves; Priscila Nicolicht; Agatha Ribeiro Mendes; Jane Da Silva; Mar Guilarte; Anete Sevciovic Grumach; Eli Mansour; Anette Bygum; João Bosco Pesquero Journal: Front Med (Lausanne) Date: 2019-02-21
Authors: Faidra Parsopoulou; Gedeon Loules; Maria Zamanakou; Dorottya Csuka; Agnes Szilagyi; Maria Kompoti; Grzegorz Porebski; Fotis Psarros; Markus Magerl; Anna Valerieva; Maria Staevska; Krystyna Obtulowicz; Marcus Maurer; Matthaios Speletas; Henriette Farkas; Anastasios E Germenis Journal: Front Allergy Date: 2022-07-07
Authors: Christian Drouet; Alberto López-Lera; Arije Ghannam; Margarita López-Trascasa; Sven Cichon; Denise Ponard; Faidra Parsopoulou; Hana Grombirikova; Tomáš Freiberger; Matija Rijavec; Camila L Veronez; João Bosco Pesquero; Anastasios E Germenis Journal: Front Allergy Date: 2022-03-31
Authors: Carina M Mathey; Carlo Maj; Annika B Scheer; Julia Fazaal; Bettina Wedi; Dorothea Wieczorek; Philipp M Amann; Harald Löffler; Lukas Koch; Clemens Schöffl; Heinrich Dickel; Nomun Ganjuur; Thorsten Hornung; Susann Forkel; Jens Greve; Gerda Wurpts; Pär Hallberg; Anette Bygum; Christian Von Buchwald; Malgorzata Karawajczyk; Michael Steffens; Julia Stingl; Per Hoffmann; Stefanie Heilmann-Heimbach; Elisabeth Mangold; Kerstin U Ludwig; Eva R Rasmussen; Mia Wadelius; Bernhardt Sachs; Markus M Nöthen; Andreas J Forstner Journal: Front Genet Date: 2022-07-18 Impact factor: 4.772