Thrombophilia Caused by Beta2-Glycoprotein I Deficiency： In Vitro Study of a Rare Mutation in APOH Gene  

作　　者：Xiao-ping ZHANG Wei ZENG Hui LIU Liang TANG Qing-yun WANG Zhi-peng CHENG Ying-ying WU Bei HU Wei SHI Yu HU 

机构地区：[1]Institute of Hematology, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China [2]Hubei Clinical and Research Center of Thrombosis and Hemostasis, Wuhan 430022, China [3]Department of Radiotherapy and Chemotherapy, Zhongnan Hospital of Wuhan University, Wuhan 430071, China [4]Department of Hematology, Renmin Hospital of Wuhan University, Wuhan 430060, China

出　　处：《Current Medical Science》2018年第2期379-385,共7页当代医学科学（英文）

摘　　要：This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.This study aimed to explore the mechanism of a novel mutation （p.Lys38Glu） in apolipoprotein H （APOH） gene causing hereditary beta2-glycoprotein I （β2GPI） deficiency and thrombosis in a proband with thrombophilia. The plasma level of β2GPI was measured by ELISA and Western blotting, and anti-β2GPI antibody by ELISA. Lupus anticoagulant （LA） was assayed using the dilute Russell viper venom time. Deficiency of the major natural anticoagulants including protein C （PC）, protein S （PS）, antithrombin （AT） and thrombomodulin （TM） was excluded from the proband. A mutation analysis was performed by amplification and sequencing of the APOH gene. Wild type and mutant （c.112A〉G） APOH expression plasmids were constructed and transfected into HEK293T cells. The results showed that the thrornbin generation capacity of the proband was higher than that of the other family members. Missense mutation p.Lys38Glu in APOH gene and LA coexisted in the proband. The mutation led to β2GPI deficiency and thrombosis by impairing the protein production and inhibiting the platelet aggregation. It was concluded that the recurrent thrombosis of the proband is associated with the coexistence ofp.Lys38Glu mutation in APOH gene and LA in plasma.

关 键 词：beta2-glycoprotein I lupus anticoagulant MUTATION apolipoprotein H THROMBOPHILIA 

分 类 号：R[医药卫生]