genetic background analysis of protein c deficiency demonstrates a recurrent mutation associated with venous thrombosis in chinese population遗传背景分析,蛋白c缺陷演示了一个频发突变在中国人口与静脉血栓形成有关.pdfVIP

Genetic Background Analysis of Protein C Deficiency Demonstrates a Recurrent Mutation Associated with Venous Thrombosis in Chinese Population Liang Tang1,2,3, Tao Guo1,2,3, Rui Yang1,2,3, Heng Mei1,2,3, Huafang Wang1,2,3, Xuan Lu1,2,3, Jianming Yu1,2,3, Qingyun Wang1,2,3, Yu Hu1,2,3* 1 Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, 2 Hubei Clinical and Research Center of Thrombosis and Hemostasis, Wuhan, Hubei, People’s Republic of China, 3 Targeted Biotherapy Key Laboratory of Ministry of Education, Wuhan, Hubei, People’s Republic of China Abstract Background: Protein C (PC) is one of the most important physiological inhibitors of coagulation proteases. Hereditary PC deficiency causes a predisposition to venous thrombosis (VT). The genetic characteristics of PC deficiency in the Chinese population remain unknown. Methods: Thirty-four unrelated probands diagnosed with hereditary PC deficiency were investigated. PC activity and antigen levels were measured. Mutation analysis was performed by sequencing the PROC gene. In silico analyses, including PolyPhen-2, SIFT, multiple sequence alignment, splicing prediction, and protein molecular modeling were performed to predict the consequences of each variant identified. One recurrent mutation and its relative risk for thrombosis in relatives were analyzed in 11 families. The recurrent mutation was subsequently detected in a case (VT patients)-control study, and the adjusted odds ratio (OR) for VT risk was calculated by logistic regression analysis. Results: A total of 18 different mutations, including 12 novel variants, were identified. One common mutation, PROC c.565C.T (rs146922325:C .T), was found in 17 of the 34 probands. The family study showed that first-degree relatives