New Gene Variants Associated with the Risk of Chronic HBV Infection

查看全文 作　　者：Mengjie [1]Fan;Jing [2,3]Wang;Sa [1]Wang;Tengyan [3]Li;Hong [3]Pan;Hankui [4,5]Liu;Huifang [4,5]Xu;Daria [6]V.Zhernakova;Stephen J.O’[6,7]Brien;Zhenru [8]Feng;Le [8]Chang;Erhei [9]Dai;Jianhua [9]Lu;Hongli [1]Xi;Yanyan [1]Yu;Jianguo [4,5]Zhang;Binbin [3]Wang;Zheng [1]Zeng

机构地区：[1]Department of Infectious Diseases,Peking University First Hospital,Beijing 100034,China;[2]Department of Medical Genetics and Development Biology,School of Medical Basic,Capital Medical University,Beijing 100069,China;[3]Center for Genetics,National Research Institute for Family Planning,Beijing 100081,China;[4]BGI-Shenzhen,Shenzhen 518083,China;[5]BGI Genomics,BGI-Shenzhen,Shenzhen 518083,China;[6]Laboratory of Genomic Diversity,Center for Computer Technologies,ITMO University,St.Petersburg,Russia 197101;[7]Guy Harvey Oceanographic Center,Halmos College of Natural Sciences and Oceanography,Nova Southeastern University,Ft Lauderdale,FL 33004,USA;[8]Department of Laboratory Medicine,Peking University First Hospital,Beijing 100034,China;[9]The Fifth Hospital of Shijiazhuang,Shijiazhuang 050024,China

出　　处：《Virologica Sinica》索引2020年第35卷第4期,共10页

基　　金：supported by grant from the International Science&Technology Cooperation Program of China(No.2014DFR31200);the National Infrastructure of Chinese Genetic Resources(YCZYPT[2017]01-6);federal funds from the National Cancer Institute,National Institutes of Health,USA(No.N01-CO12400);the National Natural Science Foundation of China(No.30671855)。 摘　　要：Some patients with chronic hepatitis B virus(HBV)infection failed to clear HBV,even persistently continue to produce antibodies to HBV.Here we performed a two stage genome wide association study in a cohort of Chinese patients designed to discover single nucleotide variants that associate with HBV infection and clearance of HBV.The first stage involved genome wide exome sequencing of 101 cases(HBsAg plus anti-HBs positive)compared with 102 control patients(antiHBs positive,HBsAg negative).Over 80%of individual sequences displayed 209 sequence coverage.Adapters,uncertain bases[10%or low-quality base calls([50%)were filtered and compared to the human reference genome hg19.In the second stage,579 chronic HBV infected cases and 439 HBV clearance controls were sequenced with selected genes from the first stage.Although there were no significant associated gene variants in the first stage,two significant gene associations were discovered when the two stages were assessed in a combined analysis.One association showed rs506121-“T”allele[within the dedicator of cytokinesis 8(DOCK8)gene]was higher in chronic HBV infection group than that in clearance group(P=0.002,OR=0.77,95%CI[0.65,0.91]).The second association involved rs2071676—A allele within the Carbonic anhydrase(CA9)gene that was significantly elevated in chronic HBV infection group compared to the clearance group(P=0.0003,OR=1.35,95%CI[1.15,1.58]).Upon replication these gene associations would suggest the influence of DOCK8 and CA9 as potential risk genetic factors in the persistence of HBV infection. 关键词：Whole exome sequencing HBV infection DOCK8 CA9 VARIATION

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New Gene Variants Associated with the Risk of Chronic HBV Infection

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