Background: Venous thrombosis (VT) is a worldwide medical problem. In order to identify individuals at high risk early, it is necessary to find more genetic risk factors. Nowadays, the studies on genetic factors of thrombosis are mainly focused on coagulation and anticoagulation factors. The exploration of other proteins involved in thrombosis and hemostasis may lead to a breakthrough.
Objectives: We used APOH as a candidate gene to investigate the existence of genetic variation that could increase the risk of thrombosis.
Methods/results: In the current study, with a resequencing method followed by a case-control study, four polymorphisms (c.-32C>A, c.422T>C, c.461G>A, and c.1004G>C) in APOH (encoding β2 -glycoprotein I) were found to be in high linkage disequilibrium, which could result in three haplotypes. The H2 heterozygotes and H3 homozygotes had approximately 1.5-fold and seven-fold increased risks for VT, respectively. The minor allele frequency in the general population was ~ 10%. In addition, H3 individuals showed a significantly decreased level of β2 -glycoprotein I, but an increased level of thrombin generation. Functional tests indicated that the mutant β2 -glycoprotein I had a significantly lower capacity to extend thrombin clotting time and increase thrombin generation potential.
Conclusions: This study revealed APOH as a new candidate gene associated with thrombosis, and further genetic research on this gene in patients in whom the cause of thrombophilia is unknown is therefore warranted.
Keywords: Beta2-Glycoprotein I; genetic polymorphisms; linkage disequilibrium; risk factors; venous thrombosis.
© 2014 International Society on Thrombosis and Haemostasis.