PMID- 34430511
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220426
IS  - 2253-5969 (Print)
IS  - 2253-5969 (Electronic)
IS  - 2253-5969 (Linking)
VI  - 8
DP  - 2021
TI  - Fine Mapping of the MHC Region Identifies Novel Variants Associated with 
      HBV-Related Hepatocellular Carcinoma in Han Chinese.
PG  - 951-961
LID - 10.2147/JHC.S321919 [doi]
AB  - INTRODUCTION: Genome-wide association studies identified susceptibility loci in 
      the major histocompatibility complex region for hepatitis B virus (HBV)-related 
      hepatocellular carcinoma (HCC). However, the causal variants underlying 
      HBV-related HCC pathogenesis remain elusive. METHODS: With a total of 1,161 
      HBV-related HCC cases and 1,353 chronic HBV carriers without HCC, we imputed 
      human leukocyte antigen (HLA) variants based on a Chinese HLA reference panel and 
      evaluated the associations of these variants with the risk of HBV-related HCC. 
      Conditional analyses were used to identify independent signals associated with 
      the risk of HBV-related HCC (P false-discovery rate (FDR) <0.20). A total of 
      14,930 variants within the MHC region were genotyped or imputed. RESULTS: We 
      identified two variants, rs114401688 (P = 1.05 x 10(-6), P(FDR) = 2.43 x 10(-3)) 
      and rs115126566 (P = 9.04 x 10(-5), P(FDR) = 1.77 x 10(-1)), that are 
      independently associated with the risk of HBV-related HCC. Single nucleotide 
      polymorphism (SNP) rs114401688 is in linkage disequilibrium with a previously 
      reported SNP rs9275319. In the current study, we found that its association with 
      HCC could be explained by HLA-DQB1*04 and HLA-DRB1*04. SNP rs115126566 is a novel 
      risk variant and may function by regulating transcriptions of HLA-DPA1/DPB1 
      through enhancer-mediated mechanisms. HLA zygosity analysis showed that 
      homozygosity at HLA-DQB1 gene is suggestively associated with a higher risk of 
      HCC (P = 0.10) and the risk was more pronounced in the older age group (age >/=50, 
      P = 0.03). DISCUSSION: Our findings further the understanding of the genetic 
      basis for HBV-related HCC predisposition in chronic HBV carriers.
CI  - (c) 2021 Mai et al.
FAU - Mai, Haoming
AU  - Mai H
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Chen, Jiaxuan
AU  - Chen J
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Chen, Haitao
AU  - Chen H
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
AD  - School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, 
      People's Republic of China.
FAU - Liu, Zhiwei
AU  - Liu Z
AD  - Division of Cancer Epidemiology and Genetics, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Huang, Guanlin
AU  - Huang G
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Wang, Jialin
AU  - Wang J
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Xiao, Qianyi
AU  - Xiao Q
AD  - School of Public Health, Fudan University, Shanghai, 200032, People's Republic of 
      China.
FAU - Ren, Weihua
AU  - Ren W
AD  - Central Laboratory, First Affiliated Hospital, Henan University of Science and 
      Technology, Luoyang, Henan Province, 471009, People's Republic of China.
FAU - Zhou, Bin
AU  - Zhou B
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Hou, Jinlin
AU  - Hou J
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
FAU - Jiang, Deke
AU  - Jiang D
AD  - State Key Laboratory of Organ Failure Research, Guangdong Key Laboratory of Viral 
      Hepatitis Research, Guangdong Institute of Liver Diseases, Department of 
      Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical 
      University, Guangzhou, 510515, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20210816
PL  - New Zealand
TA  - J Hepatocell Carcinoma
JT  - Journal of hepatocellular carcinoma
JID - 101674775
PMC - PMC8378933
OTO - NOTNLM
OT  - HBV
OT  - MHC
OT  - fine mapping
OT  - hepatocellular carcinoma
OT  - susceptibility
COIS- Professor Jinlin Hou reports personal fees from AbbVie, personal fees from 
      Arbutus, grants, personal fees from Bristol Myers Squibb, personal fees from 
      Gilead Sciences, grants, personal fees from Johnson & Johnson, personal fees from 
      Roche, outside the submitted work. The authors declare that they have no other 
      conflicts of interest in this work.
EDAT- 2021/08/26 06:00
MHDA- 2021/08/26 06:01
PMCR- 2021/08/16
CRDT- 2021/08/25 06:27
PHST- 2021/05/26 00:00 [received]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/08/25 06:27 [entrez]
PHST- 2021/08/26 06:00 [pubmed]
PHST- 2021/08/26 06:01 [medline]
PHST- 2021/08/16 00:00 [pmc-release]
AID - 321919 [pii]
AID - 10.2147/JHC.S321919 [doi]
PST - epublish
SO  - J Hepatocell Carcinoma. 2021 Aug 16;8:951-961. doi: 10.2147/JHC.S321919. 
      eCollection 2021.