New Gene Variants Associated with the Risk of Chronic HBV Infection
- PDF / 1,446,650 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 116 Downloads / 187 Views
www.virosin.org www.springer.com/12250
(0123456789().,-volV)(0123456789().,-volV)
RESEARCH ARTICLE
New Gene Variants Associated with the Risk of Chronic HBV Infection Mengjie Fan1 • Jing Wang2,3 • Sa Wang1 • Tengyan Li3 • Hong Pan3 • Hankui Liu4,5 • Huifang Xu4,5 • Daria V. Zhernakova6 • Stephen J. O’Brien6,7 • Zhenru Feng8 • Le Chang8 • Erhei Dai9 • Jianhua Lu9 • Hongli Xi1 • Yanyan Yu1 • Jianguo Zhang4,5 • Binbin Wang3 • Zheng Zeng1 Received: 5 March 2019 / Accepted: 16 January 2020 Ó Wuhan Institute of Virology, CAS 2020
Abstract 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 20 9 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. Keywords Whole exome sequencing HBV infection DOCK8 CA9 Variation
Mengjie Fan, Jing Wang and Sa Wang have contributed equally to this work.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12250-020-00200-x) contains supplementary material, which is available to authorized users. & Jianguo Zhang [email protected] & Binbin Wang [email protected] & Zheng Zeng [email protected] 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
Abbreviations ALT Alanine transaminase anti-HAV Antibody to hepatitis A virus anti-HBc Antibody to hepatitis B core antigen anti-HBe Anti
Data Loading...
