Identification of APOH polymorphisms as common genetic risk factors for venous thrombosis in the Chinese population. (23rd August 2014)

• Record Type: Journal Article
• Authors: Tang, L.; Zeng, W.; Lu, X.; Wang, Q.‐Y.; Liu, H.; Cheng, Z.‐P.; Wu, Y.‐Y.; Hu, B.; Jian, X.‐R.; Guo, T.; Wang, H.‐F.; Hu, Y.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 12:Number 10(2014:Oct.)
• Page Start: 1616
• Page End: 1625
• Publication Date: 2014-08-23
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12679
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12679-abs-0001"> <title>Summary</title> <sec id="jth12679-sec-0001" sec-type="section"> <title>Background</title> <p>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.</p> </sec> <sec id="jth12679-sec-0002" sec-type="section"> <title>Objectives</title> <p>We used <italic>APOH</italic> as a candidate gene to investigate the existence of genetic variation that could increase the risk of thrombosis.</p> </sec> <sec id="jth12679-sec-0003" sec-type="section"> <title>Methods/Results</title> <p>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 <italic>APOH</italic> (encoding β<sub>2</sub>‐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 β<sub>2</sub>‐glycoprotein I, but an increased level of thrombin generation. Functional tests indicated that the mutant β<sub>2</sub>‐glycoprotein I had a significantly lower capacity to extend thrombin clotting time and increase thrombin generation potential.</p> </sec> <sec id="jth12679-sec-0004" sec-type="section"> <title>Conclusions</title> <p>This study revealed <italic>APOH</italic> 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.</p> </sec> </abstract>