Study On The Association Between Protein S And Venous Thromboembolism In Chinese Han Population

Venous thromboemlism is a pathological condition that is attributable to genetic and environmental predispositions, including deep-vein thrombosis and its complication, pulmonary embolism. VTE is a fairly common disease, associated with a high rate of morbidity and mortality, affecting human health.According to literature, the overall annual incidence rate of venous thromboembolism is higher for men than for women,130 per 100,000,110 per 100,000, respectively. Women during childbearing years is associated with a higher incidence rates compared with men of similar age, whereas incidence rates are generally higher in men aged>45 years compared with women.Substantial disparities in the incidence of VTE have been observed among different ethnic groups. VTE incidence is the highest in individuals of African population, followed by Caucasians, intermediate in Hispanics, and the lowest in Asians. Venous thromboemlism is caused by interaction with genetic and environmental components. Acquaintance is greatly increased that genetic predispositions is different among different ethnic groups.FV Leiden and FII G20210A are common risk factor of venous thromboembolism, caused by gain-of-function mutations of procoagulant genes. But these polymorphisms are rarely common in Asian population. In recent years, anticoagulant protein deficiency is main risk factor of venous thromboembolism. So, we devote to investigate the association between the antigen and polymorphysim protein S and occurrence of venous thromboembolism. Part 1 Plasma free protein S level and risk of venous thromboembolism inChinese han populationObjectivesProtein S is an extensive-studied anticoagulation protein. Conflicting data have been observed regarding the association between the risk of venous thromboembolism and decreased free protein S level. Our aim is to:i) determine whether decreased free protein S level was associated with risk of venous thromboembolism:ii) to define the optimal free protein S level to detect subjects at risk of venous thromboembolism.Method323 venous thromboembolism patients were enrolled from September in 2013 to September in 2014 at Hubei clinical and research center of haemostasis and thrombosis, along with 352 control participants without individual or family history of thrombosis. The demographic data, general clinical data and acquired risk factors in case and control participants were collected. The case-control study stratified the levels of free protein S and evaluated the risk of venous thromboembolism in different strata of free protein S levels. Molecular basis of protein S deficiency was analyzed.ResultFree protein S deficiency was associated with venous thromboembolism:free protein S level (<6th percentile of control,<39U/dL), OR= 2.14,95%CI:1.10-4.15 and free protein S level (<2th percentile of control,<26U/dL), OR=4.39,95%CI:1.13-17.07.PROS1 was sequenced in patients and participants with the level of free.protein S< 45 U/dL. Mutation detected in 11 patients and 3 controlswith PS deficiency.ConclutionProtein S deficiency was associated with risk of venous thromboembolism, although the cutofflevel lies far below the normal range inhealthy volunteers. Genetic protein S deficiency was the relatively common risk factor of venous thromboembolism.Part 2 the association between the PROS1 gene polymorphism and risk of venous thromboembolism in Chinese han populationAimProtein S is an important anticoagulant protein.The current study found no PROS1 common polymorphism in china han population. Our aim was to investigate the association between the any genetic variant in the human protein S gene (PROS1) and susceptibility to VTE in the Chinese Han population.MethodGenetic mutation were identified through direct genomic DNA sequencing in promoter regions,15 exons and flanking intronic regions of PROS1 in 50 VTE patients?Genotype analysis of c.1494T>C were conducted in case-control population?Finally, functional studies were implemented to evaluate the effects of the variant.ResultsPROS.1 c.1494T>C was observed not to be associated with VTE(OR=0.64; 95% CI: 0.36-1.14,p=0.13). The functional studies did not show a significant difference in the anticoagulant activity of PS in c.1494T>C carriers and non-carriers.Conclusion:Our results suggested that c.1494T>C wasn't a genetic determinant of an increased risk of VTE in China han population.