PMID- 28921602
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20220317
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 67
IP  - 2
DP  - 2018 Feb
TI  - Human leukocyte antigen variants and risk of hepatocellular carcinoma modified by 
      hepatitis C virus genotypes: A genome-wide association study.
PG  - 651-661
LID - 10.1002/hep.29531 [doi]
AB  - We conducted a genome-wide association study to discover genetic variants 
      associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). 
      We genotyped 502 HCC cases and 749 non-HCC controls using the Axiom-CHB 
      genome-wide array. After identifying single-nucleotide polymorphism clusters 
      located in the human leukocyte antigen (HLA) region which were potentially 
      associated with HCC, HLA-DQB1 genotyping was performed to analyze 994 anti-HCV 
      seropositives collected in the period 1991-2013 in a community-based cohort for 
      evaluating long-term predictability of HLA variants for identifying the risk of 
      HCC. Cox proportional hazards models were used to estimate the hazard ratios and 
      95% confidence intervals of HLA genotypes for determining the aforementioned HCC 
      risk. Eight single-nucleotide polymorphisms in the proximity of HLA-DQB1 were 
      associated with HCC (P < 8.7 x 10(-8) ) in the genome-wide association study. 
      Long-term follow-up showed a significant association with HLA-DQB1*03:01 and 
      DQB1*06:02 (P < 0.05). The adjusted hazard ratios associated with HCC were 0.45 
      (0.30-0.68) and 2.11 (1.34-3.34) for DQB1*03:01 and DQB1*06:02, respectively. 
      After stratification by HCV genotypes, DQB1*03:01 showed protective effects only 
      in patients with HCV genotype 1, whereas DQB1*06:02 conferred risk of HCC only in 
      patients with HCV non-1 genotypes. HLA imputation analyses revealed that 
      HLA-DRB1*15:01, which is in linkage disequilibrium with DQB1*06:02, also 
      increased the risk of HCC (odds ratio, 1.96; 95% confidence interval, 1.31-2.93). 
      Haplotype analysis supported that DQB1*03:01 and DQB1*06:02 are primarily 
      protective and susceptible variants, respectively. Conclusion: HLA-DQB1 was 
      independently associated with HCC; HCV genotypes modified the effects of HLA-DQB1 
      on the risk of HCC. (Hepatology 2018;67:651-661).
CI  - (c) 2017 by the American Association for the Study of Liver Diseases.
FAU - Lee, Mei-Hsuan
AU  - Lee MH
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Huang, Yu-Han
AU  - Huang YH
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Chen, Hsuan-Yu
AU  - Chen HY
AD  - Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
FAU - Khor, Seik-Soon
AU  - Khor SS
AD  - Department of Human Genetics, Graduate School of Medicine, the University of 
      Tokyo, Toyo, Japan.
FAU - Chang, Ya-Hsuan
AU  - Chang YH
AD  - Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
FAU - Lin, Yu-Ju
AU  - Lin YJ
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Jen, Chin-Lan
AU  - Jen CL
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
FAU - Lu, Sheng-Nan
AU  - Lu SN
AD  - Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan.
FAU - Yang, Hwai-I
AU  - Yang HI
AD  - Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
AD  - Genomics Research Center, Academia Sinica, Taipei, Taiwan.
FAU - Nishida, Nao
AU  - Nishida N
AD  - Genome Medical Sciences Project, National Center for Global Health and Medicine, 
      Ichikawa, Japan.
FAU - Sugiyama, Masaya
AU  - Sugiyama M
AD  - Genome Medical Sciences Project, National Center for Global Health and Medicine, 
      Ichikawa, Japan.
FAU - Mizokami, Masashi
AU  - Mizokami M
AD  - Genome Medical Sciences Project, National Center for Global Health and Medicine, 
      Ichikawa, Japan.
FAU - Yuan, Yong
AU  - Yuan Y
AD  - World Wide Health Economics and Outcomes Research, Bristol-Myers Squibb, 
      Princeton, NJ.
FAU - L'Italien, Gibert
AU  - L'Italien G
AD  - Yale University, New Haven, CT.
FAU - Tokunaga, Katsushi
AU  - Tokunaga K
AD  - Department of Human Genetics, Graduate School of Medicine, the University of 
      Tokyo, Toyo, Japan.
FAU - Chen, Chien-Jen
AU  - Chen CJ
AD  - Academia Sinica, Taipei, Taiwan.
CN  - REVEAL-HCV Cohort Study Group
LA  - eng
GR  - MOST 104-2628-B-010-001-MY3/Ministry of Science and Technology, Taipei, 
      Taiwan/International
GR  - MOST 105-2628-B-010-003-MY4/Ministry of Science and Technology, Taipei, 
      Taiwan/International
GR  - Bristol-Myers Squibb Co./International
GR  - Academia Sinica, Taipei, Taiwan/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180101
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Alleles
MH  - Carcinoma, Hepatocellular/*etiology/immunology/virology
MH  - Case-Control Studies
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - HLA-DQ beta-Chains/*genetics
MH  - Haplotypes
MH  - Hepacivirus/classification/*genetics
MH  - Humans
MH  - Liver Neoplasms/*etiology/immunology/virology
MH  - *Polymorphism, Single Nucleotide
MH  - Risk
EDAT- 2017/09/19 06:00
MHDA- 2019/10/29 06:00
CRDT- 2017/09/19 06:00
PHST- 2017/05/18 00:00 [received]
PHST- 2017/09/06 00:00 [revised]
PHST- 2017/09/11 00:00 [accepted]
PHST- 2017/09/19 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2017/09/19 06:00 [entrez]
AID - 10.1002/hep.29531 [doi]
PST - ppublish
SO  - Hepatology. 2018 Feb;67(2):651-661. doi: 10.1002/hep.29531. Epub 2018 Jan 1.