Subtypes of SERPINC1 mutations and the thrombotic phenotype of inherited antithrombin deficient individuals in Chinese Han population

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. 32 years, 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. (C) 2016 Published by Elsevier Inc.