Genes associated with blood clotting

Genes associated with blood clotting
25 March 2010 | By Dr Susmita Chowdhury | Research article

Problems with clotting or coagulation of the blood may dispose to hemorrhage (excessive bleeding) or thrombosis (excessive clotting), and this can lead to stroke, heart attack, pulmonary embolism, bleeding disorders and other serious conditions, giving rise to the most common causes of mortality and morbidity in the Western world. Activated partial thromboplastin time (aPTT), which may be either prolonged or shortened, is considered to be a global test of thrombolytic tendency.

Recently researchers at the University of Edinburgh [Houlihan LM et al. Am J Hum Genet. 2010 Mar 18] aimed to identify polymorphisms causing variation in a measure of the time it takes blood to clot (called activated partial thromboplastin time, aPTT) in the general older population via genome wide association methods. A total of 1477 Scottish adults from 1921 and 1931 birth cohorts were included in initial aPTT measurements, and genotypic information from 488 individuals were used for analysis.

The scientists identified associations of genome-wide significance with relatively large effect sizes between aPTT and variants in three genes, F12, KNG1 and HRG. These genes all have important functional roles in the blood coagulation cascade, which is a series of reactions that cause blood to clot by the formation of cross-linked fibrin clot. For example, the F12 gene encodes the coagulation factor XII precursor molecule, which is involved with the initiation of blood coagulation. Mutations in any of these genes could potentially lead to coagulation disorders; for example, variation in HRG has been linked to thrombophilia, in which aPTT is prolonged.

The study findings showed that the variants in the three genes accounted for approximately 18% of the variance of aPTT which, the authors proposed to be a relatively substantial proportion.

Comment: Since the participants had an average age of 79 at the time of the study and come from the same geographical region, findings from a validation study on a younger population and different area would be of interest. The findings of this study may be followed up to establish their clinical significance while further experimental studies are required to establish the mechanisms by which these genes prolong aPTT in vitro and influence thrombosis in vivo. Overall, this study makes an important contribution to knowledge about the genetics of blood clotting, especially because so few genes seem to account for such a relatively large effect.
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