In:
International Archives of Allergy and Immunology, S. Karger AG, Vol. 174, No. 3-4 ( 2017), p. 200-204
Kurzfassung:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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 〈 i 〉 KLKB1 〈 /i 〉 -428G/A to the disease phenotype. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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 〈 i 〉 KLKB1 〈 /i 〉 -428G/A, combined or not with that of the functional 〈 i 〉 F12 〈 /i 〉 -46C/T polymorphism. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Carriers of the G allele of the 〈 i 〉 KLKB1 〈 /i 〉 -428G/A polymorphism exhibited a significantly delayed disease onset (i.e., by 4.1 years [ 〈 i 〉 p 〈 /i 〉 〈 0.001], depending on the zygocity status), while carriers of both the 〈 i 〉 KLKB1 〈 /i 〉 -428G/A and the 〈 i 〉 F12 〈 /i 〉 -46C/T polymorphism displayed an 8.8-year delay in disease onset ( 〈 i 〉 p 〈 /i 〉 〈 0.001) and a 64% lower probability of needing long-term prophylactic treatment ( 〈 i 〉 p 〈 /i 〉 = 0.019). 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 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.
Materialart:
Online-Ressource
ISSN:
1018-2438
,
1423-0097
Sprache:
Englisch
Verlag:
S. Karger AG
Publikationsdatum:
2017
ZDB Id:
1482722-0
