Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study  

作　　者：Yanghui Chen Yang Sun Zongzhe Li Chenze Li Lei Xiao Jiaqi Dai Shiyang Li Hao Liu Dong Hu Dongyang Wu Senlin Hu Bo Yu Peng Chen Ping Xu Wei Kong Dao Wen Wang 

机构地区：[1]Division of Cardiology,Department of Internal Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders,Huazhong University of Science and Technology,Wuhan 430030,China [3]The First Affiliated Hospital of the Medical College,Shihezi University,Shihezi 832008,China [4]State Key Laboratory of Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Beijing Institute of Lifeomics,Beijing 102206,China [5]Department of Physiology and Pathophysiology,School of Basic Medical Sciences,Peking University,Beijing 100191,China

出　　处：《Frontiers of Medicine》2021年第3期438-447,共10页医学前沿（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.91839302,91439203,and 81700413);the National Key R&D Program of China(No.2017YFC0909400);the Municipal Science and Technology Major Project(No.2017SHZDZX01).

摘　　要：Thoracic aortic dissection(TAD)without familial clustering or syndromic features is known as sporadic TAD(STAD).So far,the genetic basis of STAD remains unknown.Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population(N=637).After population structure and genetic relationship and ancestry analyses,we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD.We found that COL3A1 was significantly relevant to STAD(P=7.35×10^(−6))after 10000 times permutation test(P=2.49×10^(−3)).Moreover,another independent cohort,including 423 cases and 734 non-STAD subjects(N=1157),replicated our results(P=0.021).Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues,and its expression was related to the extracellular matrix(ECM)pathway.Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway.We wanted to expand the knowledge of the genetic basis and pathology of STAD,which may further help in providing better genetic counseling to the patients.

关 键 词：sporadic thoracic aortic dissection exome sequencing gene COL3A1 case–control study extracellular matrix 

分 类 号：R543.1[医药卫生—心血管疾病]