title: Genetics of fibrin clot structure: a twin study.
abstract: Coronary artery thrombosis following plaque rupture is an important feature of myocardial infarction, and studies have highlighted the role of coagulation in this condition. Although genetic and environmental influences on the variance in coagulation protein concentrations have been reported, there are no data on the heritability of structure/function of the final phenotype of the coagulation cascade, the fibrin clot. To assess genetic and environmental contributions to fibrin structure, permeation and turbidity studies were performed in 137 twin pairs (66 monozygotic, 71 dizygotic). The environmental influence (e2) on pore size (Ks) (e2 = 0.61 [95% confidence interval (CI), 0.45-0.80]) and fiber size (e2 = 0.54 [95% CI, 0.39-0.73]) was greater than the heritability (h2 = 0.39 [95% CI, 0.20-0.55] and 0.46 [95% CI, 0.27-0.62], respectively). After correction for fibrinogen levels, the environmental effect persisted for Ks (e2 = 0.61), but genetic influence assumed a greater importance in determining fiber size (h2 = 0.73). Multivariate analysis revealed an overlap in the influence of genetic and environmental factors on fibrinogen levels, Ks, and fiber size. Factor XIII B subunit showed environmental and genetic correlation with fibrinogen and fiber size and a genetic correlation with Ks. The results indicate that genetic and environmental influences are important in determining fibrin clot structure/function.
authors: Academic Unit of Molecular Vascular Medicine, General Infirmary, Leeds, United Kingdom.
authors: Emma J
authors: EJ
authors: Dunn
authors: Robert A
authors: RA
authors: Ariëns
authors: Marlies
authors: M
authors: de Lange
authors: Harold
authors: H
authors: Snieder
authors: John H
authors: JH
authors: Turney
authors: Timothy D
authors: TD
authors: Spector
authors: Peter J
authors: PJ
authors: Grant
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001777:Blood Coagulation / Q000235:genetics*; D003331:Coronary Vessels / Q000473:pathology*; D004200:Diseases in Twins; D004777:Environment; D005176:Factor XIII / Q000737:chemistry; D005260:Female; D005337:Fibrin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D013927:Thrombosis / Q000235:genetics*; D013997:Time Factors; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D005176:Factor XIII; C054380:factor XIIIb