title: Subtypes of SERPINC1 mutations and the thrombotic phenotype of inherited antithrombin deficient individuals in Chinese Han population.
abstract: Inherited antithrombin (AT) deficiency is a rare autosomal disease that could increase the risk of venous thromboembolism (VTE) and usually caused by mutations of SERPINC1. Although a number of mutations of SERPINC1 have been reported in Chinese Han population, the impact of different subtypes of these mutations on the thrombotic phenotype is still unknown. Here, we performed a retrospective cohort study including 169 AT patients from 63 families to compare the clinical features between null mutation carriers and missense mutation carriers. We found that patients carrying null mutations have a higher risk of VTE (HR 2.29, 95% CI 1.16-4.69, P=0.02 adjusted for sex and VTE family history) and earlier median onset age of VTE (27 vs. 32years, P=0.045) as well as lower AT activities (47.6±1.0% vs. 59.1±2.3%, P<0.001) than those with missense mutations. We also observed that thrombus location sites showed no difference between null mutation carriers and missense mutation carriers, gene locations of the mutations did not relate with the incidence rate of VTE. This study demonstrated that different types of SERPINC1 mutations may play different roles in the development of VTE and should be considered in the prevention of VTE.
authors.affiliation: Institute of Hypertension, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Hypertension, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: cuiguanglin@tjh.tjmu.edu.cn.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Cui
authors.affiliation: Institute of Hypertension, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Institute of Hypertension, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D000328:Adult; D017668:Age of Onset; D000990:Antithrombin III / Q000235:genetics*; D020152:Antithrombin III Deficiency / Q000235:genetics*; D044466:Asian People; D005260:Female; D006801:Humans; D000073658:Loss of Function Mutation; D008297:Male; D008487:Medical History Taking; D020125:Mutation, Missense; D010641:Phenotype; D012189:Retrospective Studies; D013927:Thrombosis / Q000235:genetics*
chemical_list: C542513:SERPINC1 protein, human; D000990:Antithrombin III
keywords: Antithrombin deficiency; Genetics; Mutation; Phenotype; Venous thromboembolism