C-B4-02: Determining Genetic Risk Factors for Post- Hospitalization development of Deep-Vein Thrombosis

Abstract

Background: Venothromboembolism (VTE) including deep venous thrombosis (DVT) and pulmonary embolism (PE) are significant health care problems. A highly specific DVT risk stratification model requires a combination of genetic, environmental, clinical, laboratory and radiographic measurements. Genetic factors associated with DVT in post-hospitalized medical and surgical patients are incompletely understood. Aim: Using the Personalized Medicine Research Project (PMRP) population and a limited number of disease associated polymorphisms were used to determine whether these markers were associated with DVT in the post-hospitlalization period. Methods: Marshfield Clinic patients who have experienced a DVT between 1999 and 2007 enrolled in the PMRP were genotyped for 52 disease associated polymorphisms (N=1124). From these individuals we identified 451 who experienced a DVT after post-hospitalization for a medical (N=164) or surgical (N=136) procedure or both (N=151). This cohort was compared to the PMRP population that had a recorded hospitalization without a post-hospitalization DVT during the same time period (N=1662). Results: Polymorphisms in APOB (rs1042031), PLAU (rs2227564), HTR2A (rs6313) and the Vitamin D receptor haplotype (rs731236 and rs7975232) were associated with post hospitalization DVT. When the population that incurred a DVT was stratified by DVT category (post medical, post surgical or both), the PLAU polymorphism was most strongly associated with individuals experiencing a DVT post-surgically. Vitamin D receptor haplotype was significantly associated with individuals experiencing both post medical and post surgical DVTs, and polymorphisms associated with cholesterol and lipid levels were most likely to be associated with post-medical DVTs. Conclusions: This hypothesis generating study demonstrates that there are many polymorphisms that are associated with DVT that have yet to be characterized. Categorization of associated DVT polymorphisms will involve careful interrogation of both the environmental conditions as well as genetic alleles of individuals. Genes such as PLAU, HTR2A, and Vitamin D are just now being investigated for thrombogenic effects and in future may lead to a better understanding of indentifying the individuals at risk for a DVT post hospitilization.