Heritability of clot formation, morphology, and lysis: the EuroCLOT study.
OBJECTIVE
The relative balance between clot formation and fibrinolysis is considered to reflect thrombotic potential following vascular injury. The aims of the present study were to (1) to determine the contribution of genetic and environmental factors to variance in measures of clot structure/function in the Leeds Family Study, and (2) to determine the relationship between measures of clot structure/function and cardiovascular risk.


RESULTS
Using high throughput turbidimetric assays, heritabilities of measures of clot formation, clot structure, and clot lysis were approximately 0.30. Fibrinogen contributed to variance in all measures and plasminogen activator inhibitor-1 to variance in lysis variables. Subjects at increased cardiovascular risk due to the presence of the metabolic syndrome (MetS) had increased clot density (MaxAbs(C): 0.358 [0.340, 0.375]au) and prolonged lysis times (Lys(T): 510 [6569, 7939]s) compared with those without MetS (MaxAbs(C): 0.319 [0.310, 0.328]au, P=0.003; Lys(T): 7221 [4884, 5328]s, P<0.001). Furthermore, measures of clot structure/function increased progressively with increasing number of MetS components.


CONCLUSIONS
This study indicates that genetic factors contribute modestly to variance in clot structure/function and that clot structure/function is related to presence of the MetS and number of MetS components. Identification of the genetic and environmental factors influencing clot structure/function may further our understanding of the underlying factors predisposing to cardiovascular disease.
Carter
Angela M
AM
Academic Unit of Molecular Vascular Medicine, The LIGHT Laboratories, University of Leeds. Leeds LS2 9JT, UK.
Cymbalista
Charlotte M
CM
Spector
Tim D
TD
Grant
Peter J
PJ
D000328:Adult; D001777:Blood Coagulation / Q000235:genetics*; D001780:Blood Coagulation Tests / Q000379:methods; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D005060:Europe; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D010375:Pedigree; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000150:complications / Q000235:genetics*; D013997:Time Factors
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D005340:Fibrinogen