创伤后深静脉血栓形成遗传危险因素的全基因组关联分析  

Genome wide association study on genetic risk factors of deep vein thrombosis after trauma

作　　者：章文洁 苏玉 卢山 陈玉莹 曹翔宇 刘蕾 杨丽[4] 吴俊 ZHANG Wenje;SU Yu;LU Shan;CHEN Yuying;CAO Xiangyu;LIU Lei;YANG Li;WU Jun(Department of Clinical Laboratory,Beijing Jishuitan Hospital,Capital Medical University,Beijing 100035;Department of Clinical Laboratory,Peking University Fourth School of Clinical Medicine,Bejing 100035;Department of Clinical Laboratory,Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430077,Hubei;Chongqing Institute of Green and Intelligent Technology,Chinese Academy of Sciences,Chongqing 400714,China)

机构地区：[1]首都医科大学附属北京积水潭医院医学检验中心,北京100035 [2]北京大学第四临床医学院医学检验中心,北京100035 [3]华中科技大学同济医学院附属梨园医院检验科,武汉430077 [4]中国科学院重庆绿色智能技术研究院,重庆400714

出　　处：《临床检验杂志》2024年第2期126-131,共6页Chinese Journal of Clinical Laboratory Science

摘　　要：目的探究创伤后深静脉血栓形成(DVT)的遗传危险因素。方法采用巢式病例对照研究。纳入50名创伤性下肢骨折后发生DVT患者和50名未发生DVT患者,两组患者的性别、年龄、骨折部位相匹配。创伤患者于术前行静脉造影检查以诊断是否发生DVT。应用全基因组关联分析(GWAS)筛选创伤性下肢骨折后术前DVT的遗传危险因素。用于GWAS的基因组DNA从白细胞中提取。结果应用GWAS评估144个兴趣基因,包含2662个单核苷酸变异(SNV),与表型之间的相关性。共发现10个基因与创伤后DVT发生显著相关:止血机制辅因子,包括THBD、F5、SERPIND1、ITGA2,维生素K依赖(VKD)羧化相关因子,包括GGCX、CALU,细胞色素P450家族成员,包括CYP1A1、CYP3A4、CYP2C19、CYP2B6。结论创伤性下肢骨折后DVT可能受止血机制辅因子、VKD羧化相关因子和细胞色素P450家族成员的调控。Objective To investigate the genetic risk factors of deep vein thrombosis(DVT)after trauma.Methods In a nested case-control study,50 patients with DVT after traumatic lower extremity fractures and 50 patients without DVT were recruited.The two groups were matched with gender,age and fracture sites.Preoperative venography was performed to diagnose DVT in trauma patients.Genome wide association study(GWAS)was used to investigate the genetic risk factors for preoperative DVT after traumatic lower extremity fractures.Genomic DNA in leukocytes from blood sample was extracted and used for GWAS.Results GWAS was conducted based on 2662 single nucleotide variants(SNV)which were dispersed in 144 interested genes.Ten genes were found to have significant association with trauma-related DVT,including cofactors of hemostasis mechanism,i.e.,THBD,F5,SERPINDI and ITGA2,the factors related to vitamin K-dependent(VKD)carboxylation,i.e.,GGCX and CALU,and the members of cytochrome P450 family,i.e.,CYP1Al,CYP3A4,CYP2C19 and CYP2B6.Conclusion DVT after trauma might be regulated by the cofactors of hemostasis mechanism,the factors related to VKD carboxylation and the members of cytochrome P450 family.The results of our study may provide reference and inspiration for genetic susceptibility of preoperative DVT after trauma.

关 键 词：深静脉血栓形成 创伤 下肢骨折 全基因组关联分析 遗传危险因素 

分 类 号：R446[医药卫生—诊断学]