Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort.

Autor:	Borràs N; Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain.; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain., Garcia-Martínez I; Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain.; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain., Batlle J; Department of Hematology, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain., Pérez-Rodríguez A; Department of Hematology, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain., Parra R; Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain.; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain., Altisent C; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain., López-Fernández MF; Department of Hematology, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain., Costa Pinto J; Department of Hematology, Complexo Hospitalario Universitario A Coruña, INIBIC, A Coruña, Spain., Batlle-López F; Department of Research, Lapisoft SA, A Coruña, Spain., Cid AR; Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Bonanad S; Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Cabrera N; Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Moret A; Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Mingot-Castellano ME; Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain.; Hospital Universitario Virgen del Rocio, Sevilla, Spain., Navarro N; Department of Hematology, Hospital Universitario Dr. Negrín, Las Palmas de Gran Canaria, Spain., Pérez-Montes R; Department of Hematology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., Marcellini S; Department of Hematology, Salud Castilla y León, Segovia, Spain., Moreto A; Department of Hematology, Hospital Universitario Cruces, Barakaldo, Spain., Herrero S; Department of Hematology, Hospital Universitario de Guadalajara, Guadalajara, Spain., Soto I; Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain., Fernández-Mosteirín N; Department of Hematology, Hospital Universitario Miguel Servet, Zaragoza, Spain., Jiménez-Yuste V; Department of Hematology, Hospital Universitario La Paz, Madrid, Spain., Alonso N; Department of Hematology, Hospital Infanta Cristina, Badajoz, Spain., de Andrés-Jacob A; Department of Hematology, Complexo Hospitalario Universitario Santiago de Compostela, Spain., Fontanes E; Department of Hematology, Hospital Universitario Lucus Augusti, Lugo, Spain., Campos R; Department of Hematology, Hospital Jerez de la Frontera, Cádiz, Spain., Paloma MJ; Department of Hematology, Hospital Virgen del Camino, Pamplona, Spain., Bermejo N; Department of Hematology, Hospital San Pedro de Alcántara, Cáceres, Spain., Berrueco R; Department of Hematology, Hospital Sant Joan de Deu, Barcelona, Spain., Mateo J; Department of Hematology, Hospital Sta Creu i St Pau, Barcelona, Spain., Arribalzaga K; Department of Hematology, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Marco P; Department of Hematology, Hospital General de Alicante, Alicante, Spain., Palomo Á; Department of Hematology, Hospital Regional Universitario de Málaga, Málaga, Spain., Castro Quismondo N; Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain., Iñigo B; Department of Hematology, Hospital Clínico San Carlos, Madrid, Spain., Del Mar Nieto M; Department of Hematology, Complejo Hospitalario de Jaén, Jaén, Spain., Vidal R; Department of Hematology, Fundación Jiménez Díaz, Madrid, Spain., Martínez MP; Department of Hematology, Hospital Nuestra Sra. de Sonsoles, Ávila, Spain., Aguinaco R; Department of Hematology, Hospital Joan XXIII, Tarragona, Spain., Tenorio M; Department of Hematology, Hospital Ramón y Cajal, Madrid, Spain., Ferreiro M; Department of Hematology, Hospital Montecelo, Pontevedra, Spain., García-Frade J; Department of Hematology, Hospital Río Hortega, Valladolid, Spain., Rodríguez-Huerta AM; Department of Hematology, Hospital Gregorio Marañón, Madrid, Spain., Cuesta J; Department of Hematology, Hospital Virgen de la Salud, Toledo, Spain., Rodríguez-González R; Department of Hematology, Hospital Severo Ochoa, Madrid, Spain., García-Candel F; Department of Hematology, Hospital Universitario Virgen Arrixaca, Murcia, Spain., Dobón M; Department of Hematology, Hospital Lozano Blesa, Zaragoza, Spain., Aguilar C; Department of Hematology, Hospital Santa Bárbara, Soria, Spain., Corrales I; Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain.; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain., Vidal F; Congenital Coagulopathies, Banc de Sang i Teixits, Barcelona, Spain.; Transfusional Medicine, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona (VHIR-UAB), Barcelona, Spain.; CIBER de Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain.
Jazyk:	angličtina
Zdroj:	Thrombosis and haemostasis [Thromb Haemost] 2020 Mar; Vol. 120 (3), pp. 437-448. Date of Electronic Publication: 2020 Mar 05.
DOI:	10.1055/s-0040-1702227
Abstrakt:	The clinical diagnosis of von Willebrand disease (VWD), particularly type 1, can be complex because several genetic and environmental factors affect von Willebrand factor (VWF) plasma levels. An estimated 60% of the phenotypic variation is attributable to hereditary factors, with the ABO blood group locus being the most influential. However, recent studies provide strong evidence that nonsynonymous single nucleotide variants (SNVs) contribute to VWF and factor VIII phenotypic variability in healthy individuals. This study aims to investigate the role of common VWF SNVs on VWD phenotype by analyzing data from 219 unrelated patients included in the "Molecular and Clinical Profile of von Willebrand Disease in Spain project." To that end, generalized linear mixed-effects regression models were fitted, and additive and epistatic analyses, and haplotype studies were performed, considering five VWD-related measures (bleeding score, VWF:Ag, VWF:RCo, factor VIII:C, and VWF:CB). According to these analyses, homozygotes: for p.Thr789Ala(C) would be expected to show 39% higher VWF:Ag levels; p.Thr1381Ala(C), 27% lower VWF:Ag levels; and p.Gln852Arg(C), 52% lower VWF:RCo levels. Homozygotes for both p.Thr789Ala(C) and p.Gln852Arg(T) were predicted to show 185% higher VWF:CB activity, and carriers of two copies of the p.Thr1381Ala(T)/p.Gln852Arg(T) haplotype would present a 100% increase in VWF:RCo activity. These results indicate a substantial effect of common VWF variation on VWD phenotype. Although additional studies are needed to determine the true magnitude of the effects of SNVs on VWF , these findings provide new evidence regarding the contribution of common variants to VWD, which should be taken into account to enhance the accuracy of the diagnosis and classification of this condition. ClinicalTrials.gov identifier: NCT02869074. Competing Interests: None declared. (Georg Thieme Verlag KG Stuttgart · New York.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu