Fengxue Yu1, Ning Ma2, Xiaolin Zhang3, Suzhai Tian4, Lianxia Geng4, Weili Xu5, Mingbang Wang6, Yuan Jia7, Xuechen Liu8, Junji Ma8, Yuan Quan9, Chaojun Zhang10, Lina Guo10, Wenting An10, Dianwu Liu3. 1. Department of Science and Technology, The Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. Electronic address: fengxue2002yu202356@hotmail.com. 2. Department of Social Medicine and Health Care Management, Hebei Medical University, Shijiazhuang, China. 3. Division of Epidemiology, School of Public Health, Hebei Medical University, Shijiazhuang, China. 4. Department of Science and Technology, The Hebei Key Laboratory of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. 5. Department of Pediatric Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China. 6. Shenzhen Following Precision Medical Research institute, Shenzhen, Guangdong, China. 7. Department of Infectious Disease Control, The Second Hospital of Hebei Medical University, Shijiazhuang, China. 8. Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China. 9. Department of Infectious Disease, Hebei Chest Hospital, Shijiazhuang, China. 10. Department of Central Laboratory, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Abstract
BACKGROUND & AIMS: Chronic hepatitis B virus (HBV) infection is a global health problem and the outcome are associated with both viral factors and host genetic factors. High Throughput Sequencing (HTS) technology were used to identify variants associated with liver disease. METHODS: Fifty-five Chronic hepatitis B (CHB) patients, fifty-three self-healing HBV (SH) patients and 53 healthy controls (HC) were recruited, 404 cytokine and cytokine receptor related genes were captured and sequenced at high depth (>900X), both variant (Fischer's exact test, P value < 0.05) and gene (SKAT-O gene level test, adjust P value < 0.05) level association were used to identify variants and genes associated with CHB. RESULTS: Total 5083 variants have been detected, fifty-four variants were found associated with CHB, most (29/32) variants were located in HLA region, including HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 and HLA-DRB5. Several missense variants were found associated with CHB, including p.E226K in PVR (poliovirus receptor), p.E400A and p.C431R in IL4R (interleukin 4 receptor). Four variants located in 3'UTR (untranslated region) have also been found associated with CHB. CONCLUSION: Our study revealed that high through target region sequencing, combined with association analysis at variant and gene level, would be a good way to found variants and genes associated with CHB even at small sample size. Our data implied that chronic hepatitis B patients who carry these variants need intensive monitoring.
BACKGROUND & AIMS:Chronic hepatitis B virus (HBV) infection is a global health problem and the outcome are associated with both viral factors and host genetic factors. High Throughput Sequencing (HTS) technology were used to identify variants associated with liver disease. METHODS: Fifty-five Chronic hepatitis B (CHB) patients, fifty-three self-healing HBV (SH) patients and 53 healthy controls (HC) were recruited, 404 cytokine and cytokine receptor related genes were captured and sequenced at high depth (>900X), both variant (Fischer's exact test, P value < 0.05) and gene (SKAT-O gene level test, adjust P value < 0.05) level association were used to identify variants and genes associated with CHB. RESULTS: Total 5083 variants have been detected, fifty-four variants were found associated with CHB, most (29/32) variants were located in HLA region, including HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DQB2, HLA-DRB1 and HLA-DRB5. Several missense variants were found associated with CHB, including p.E226K in PVR (poliovirus receptor), p.E400A and p.C431R in IL4R (interleukin 4 receptor). Four variants located in 3'UTR (untranslated region) have also been found associated with CHB. CONCLUSION: Our study revealed that high through target region sequencing, combined with association analysis at variant and gene level, would be a good way to found variants and genes associated with CHB even at small sample size. Our data implied that chronic hepatitis Bpatients who carry these variants need intensive monitoring.