OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes. METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17). CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.
OBJECTIVE: Fibrin makes up the structural basis of an occlusive arterial thrombus, and variability in fibrin phenotype relates to cardiovascular risk. The aims of the current study from the EU consortium EuroCLOT were to (1) determine the heritability of fibrin phenotypes and (2) identify QTLs associated with fibrin phenotypes. METHODS AND RESULTS: 447 dizygotic (DZ) and 460 monozygotic (MZ) pairs of healthy UK white female twins and 199 DZ twin pairs from Denmark were studied. D-dimer, an indicator of fibrin turnover, was measured by ELISA and measures of clot formation, morphology, and lysis were determined by turbidimetric assays. Heritability estimates and genome-wide linkage analysis were performed. Estimates of heritability for d-dimer and turbidometric variables were in the range 17% to 46%, with highest levels for maximal absorbance which provides an estimate of clot density. Genome-wide linkage analysis revealed 6 significant regions with LOD >3 on 5 chromosomes (5, 6, 9, 16, and 17). CONCLUSIONS: The results indicate a significant genetic contribution to variability in fibrin phenotypes and highlight regions in the human genome which warrant further investigation in relation to ischemic cardiovascular disorders and their therapy.
Authors: J P Collet; D Park; C Lesty; J Soria; C Soria; G Montalescot; J W Weisel Journal: Arterioscler Thromb Vasc Biol Date: 2000-05 Impact factor: 8.311
Authors: J P Collet; Y Allali; C Lesty; M L Tanguy; J Silvain; A Ankri; B Blanchet; R Dumaine; J Gianetti; L Payot; J W Weisel; G Montalescot Journal: Arterioscler Thromb Vasc Biol Date: 2006-08-17 Impact factor: 8.311
Authors: Karolina Aberg; Feng Dai; Guangyun Sun; Ember Keighley; Subba Rao Indugula; Linda Bausserman; Satupaitea Viali; John Tuitele; Ranjan Deka; Daniel E Weeks; Stephen T McGarvey Journal: J Lipid Res Date: 2008-07-01 Impact factor: 5.922
Authors: Lu-Chen Weng; Weihong Tang; Stephen S Rich; Nicholas L Smith; Susan Redline; Christopher J O'Donnell; Saonli Basu; Alexander P Reiner; Joseph A Delaney; Russell P Tracy; Cameron D Palmer; Taylor Young; Qiong Yang; Aaron R Folsom; Mary Cushman Journal: Thromb Res Date: 2014-05-20 Impact factor: 3.944
Authors: M E Meltzer; S J Hasstedt; C Y Vossen; P W Callas; Ph G DE Groot; F R Rosendaal; T Lisman; E G Bovill Journal: J Thromb Haemost Date: 2011-07 Impact factor: 5.824
Authors: V P Diego; L Almasy; D L Rainwater; M C Mahaney; A G Comuzzie; S A Cole; R P Tracy; M P Stern; J W Maccluer; J Blangero Journal: Int J Vasc Med Date: 2010-06-27
Authors: Nicholas L Smith; Jennifer E Huffman; David P Strachan; Jie Huang; Abbas Dehghan; Stella Trompet; Lorna M Lopez; So-Youn Shin; Jens Baumert; Veronique Vitart; Joshua C Bis; Sarah H Wild; Ann Rumley; Qiong Yang; Andre G Uitterlinden; David J Stott; Gail Davies; Angela M Carter; Barbara Thorand; Ozren Polašek; Barbara McKnight; Harry Campbell; Alicja R Rudnicka; Ming-Huei Chen; Brendan M Buckley; Sarah E Harris; Annette Peters; Drazen Pulanic; Thomas Lumley; Anton J M de Craen; David C Liewald; Christian Gieger; Susan Campbell; Ian Ford; Alan J Gow; Michelle Luciano; David J Porteous; Xiuqing Guo; Naveed Sattar; Albert Tenesa; Mary Cushman; P Eline Slagboom; Peter M Visscher; Tim D Spector; Thomas Illig; Igor Rudan; Edwin G Bovill; Alan F Wright; Wendy L McArdle; Geoffrey Tofler; Albert Hofman; Rudi G J Westendorp; John M Starr; Peter J Grant; Mahir Karakas; Nicholas D Hastie; Bruce M Psaty; James F Wilson; Gordon D O Lowe; Christopher J O'Donnell; Jacqueline C M Witteman; J Wouter Jukema; Ian J Deary; Nicole Soranzo; Wolfgang Koenig; Caroline Hayward Journal: Circulation Date: 2011-04-18 Impact factor: 29.690
Authors: Frances M K Williams; Angela M Carter; Pirro G Hysi; Gabriela Surdulescu; Dylan Hodgkiss; Nicole Soranzo; Matthew Traylor; Steve Bevan; Martin Dichgans; Peter M W Rothwell; Cathie Sudlow; Martin Farrall; Kaisa Silander; Mari Kaunisto; Peter Wagner; Olli Saarela; Kari Kuulasmaa; Jarmo Virtamo; Veikko Salomaa; Philippe Amouyel; Dominique Arveiler; Jean Ferrieres; Per-Gunnar Wiklund; M Arfan Ikram; Albert Hofman; Giorgio B Boncoraglio; Eugenio A Parati; Anna Helgadottir; Solveig Gretarsdottir; Unnur Thorsteinsdottir; Gudmar Thorleifsson; Kari Stefansson; Sudha Seshadri; Anita DeStefano; Andreas Gschwendtner; Bruce Psaty; Will Longstreth; Braxton D Mitchell; Yu-Ching Cheng; Robert Clarke; Marco Ferrario; Joshua C Bis; Christopher Levi; John Attia; Elizabeth G Holliday; Rodney J Scott; Myriam Fornage; Pankaj Sharma; Karen L Furie; Jonathan Rosand; Mike Nalls; James Meschia; Thomas H Mosely; Alun Evans; Aarno Palotie; Hugh S Markus; Peter J Grant; Tim D Spector Journal: Ann Neurol Date: 2013-01 Impact factor: 10.422