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Next-Generation Sequencing and In Vitro Expression Study of ADAMTS13 Single Nucleotide Variants in Deep Vein Thrombosis.

التفاصيل البيبلوغرافية
العنوان: Next-Generation Sequencing and In Vitro Expression Study of ADAMTS13 Single Nucleotide Variants in Deep Vein Thrombosis.
المؤلفون: Maria Teresa Pagliari, Luca A Lotta, Hugoline G de Haan, Carla Valsecchi, Gloria Casoli, Silvia Pontiggia, Ida Martinelli, Serena M Passamonti, Frits R Rosendaal, Flora Peyvandi
المصدر: PLoS ONE, Vol 11, Iss 11, p e0165665 (2016)
بيانات النشر: Public Library of Science (PLoS), 2016.
سنة النشر: 2016
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Deep vein thrombosis (DVT) genetic predisposition is partially known.This study aimed at assessing the functional impact of nine ADAMTS13 single nucleotide variants (SNVs) previously reported to be associated as a group with DVT in a burden test and the individual association of selected variants with DVT risk in two replication studies.Wild-type and mutant recombinant ADAMTS13 were transiently expressed in HEK293 cells. Antigen and activity of recombinant ADAMTS13 were measured by ELISA and FRETS-VWF73 assays, respectively. The replication studies were performed in an Italian case-control study (Milan study; 298/298 patients/controls) using a next-generation sequencing approach and in a Dutch case-control study (MEGA study; 4306/4887 patients/controls) by TaqMan assays.In vitro results showed reduced ADAMTS13 activity for three SNVs (p.Val154Ile [15%; 95% confidence interval [CI] 14-16], p.Asp187His [19%; 95%[CI] 17-21], p.Arg421Cys [24%; 95%[CI] 22-26]) similar to reduced plasma ADAMTS13 levels of patients carriers for these SNVs. Therefore these three SNVs were interrogated for risk association. The first replication study identified 3 heterozygous carriers (2 cases, 1 control) of p.Arg421Cys (odds ratio [OR] 2, 95%[CI] 0.18-22.25). The second replication study identified 2 heterozygous carriers (1 case, 1 control) of p.Asp187His ([OR] 1.14, 95%[CI] 0.07-18.15) and 10 heterozygous carriers (4 cases, 6 controls) of p.Arg421Cys ([OR] 0.76, 95%[CI] 0.21-2.68).Three SNVs (p.Val154Ile, p.Asp187His and p.Arg421Cys) showed reduced ex vivo and in vitro ADAMTS13 levels. However, the low frequency of these variants makes it difficult to confirm their association with DVT.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
47369310
Relation: http://europepmc.org/articles/PMC5089687?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0165665
URL الوصول: https://doaj.org/article/cc527532b05d473693103138b7302427
رقم الأكسشن: edsdoj.527532b05d473693103138b7302427
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
47369310
DOI:10.1371/journal.pone.0165665