PMID- 24376798
OWN - NLM
STAT- MEDLINE
DCOM- 20141013
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - HLA-DQB1*03 confers susceptibility to chronic hepatitis C in Japanese: a 
      genome-wide association study.
PG  - e84226
LID - 10.1371/journal.pone.0084226 [doi]
LID - e84226
AB  - Hepatitis C virus (HCV) establishes a chronic infection in 70-80% of infected 
      individuals. Many researchers have examined the effect of human leukocyte antigen 
      (HLA) on viral persistence because of its critical role in the immune response 
      against exposure to HCV, but almost all studies have proven to be inconclusive. 
      To identify genetic risk factors for chronic HCV infection, we analyzed 458,207 
      single nucleotide polymorphisms (SNPs) in 481 chronic HCV patients and 2,963 
      controls in a Japanese cohort. Next, we performed a replication study with an 
      independent panel of 4,358 cases and 1,114 controls. We further confirmed the 
      association in 1,379 cases and 25,817 controls. In the GWAS phase, we found 17 
      SNPs that showed suggestive association (P < 1 x 10(-)(5)). After the first 
      replication study, we found one intronic SNP in the HLA-DQ locus associated with 
      chronic HCV infection, and when we combined the two studies, the association 
      reached the level of genome-wide significance. In the second replication study, 
      we again confirmed the association (P(combined) = 3.59 x 10(-)(1)(6), odds ratio [OR] = 
      0.79). Subsequent analysis revealed another SNP, rs1130380, with a stronger 
      association (OR=0.72). This nucleotide substitution causes an amino acid 
      substitution (R55P) in the HLA-DQB1 protein specific to the DQB1*03 allele, which 
      is common worldwide. In addition, we confirmed an association with the previously 
      reported IFNL3-IFNL4 locus and propose that the effect of DQB1*03 on HCV 
      persistence might be affected by the IFNL4 polymorphism. Our findings suggest 
      that a common amino acid substitution in HLA-DQB1 affects susceptibility to 
      chronic infection with HCV in the Japanese population and may not be independent 
      of the IFNL4 genotype.
FAU - Miki, Daiki
AU  - Miki D
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Ochi, Hidenori
AU  - Ochi H
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Takahashi, Atsushi
AU  - Takahashi A
AD  - Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, 
      RIKEN, Yokohama, Japan.
FAU - Hayes, C Nelson
AU  - Hayes CN
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Urabe, Yuji
AU  - Urabe Y
AD  - Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute 
      of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Abe, Hiromi
AU  - Abe H
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan.
FAU - Kawaoka, Tomokazu
AU  - Kawaoka T
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Tsuge, Masataka
AU  - Tsuge M
AD  - Liver Research Project Center, Hiroshima University, Hiroshima, Japan ; Natural 
      Science Center for Basic Research and Development, Hiroshima University, 
      Hiroshima, Japan.
FAU - Hiraga, Nobuhiko
AU  - Hiraga N
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Imamura, Michio
AU  - Imamura M
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Kawakami, Yoshiiku
AU  - Kawakami Y
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Aikata, Hiroshi
AU  - Aikata H
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
FAU - Takahashi, Shoichi
AU  - Takahashi S
AD  - Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute 
      of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan ; Liver 
      Research Project Center, Hiroshima University, Hiroshima, Japan.
FAU - Akuta, Norio
AU  - Akuta N
AD  - Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
FAU - Suzuki, Fumitaka
AU  - Suzuki F
AD  - Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
FAU - Ikeda, Kenji
AU  - Ikeda K
AD  - Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
FAU - Kumada, Hiromitsu
AU  - Kumada H
AD  - Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
FAU - Karino, Yoshiyasu
AU  - Karino Y
AD  - Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan.
FAU - Toyota, Joji
AU  - Toyota J
AD  - Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan.
FAU - Tsunoda, Tatsuhiko
AU  - Tsunoda T
AD  - Laboratory for Medical Science Mathematics, Center for Integrative Medical 
      Sciences, RIKEN, Yokohama, Japan.
FAU - Kubo, Michiaki
AU  - Kubo M
AD  - Laboratory for Genotyping Development, Center for Integrative Medical Sciences, 
      RIKEN, Yokohama, Japan.
FAU - Kamatani, Naoyuki
AU  - Kamatani N
AD  - Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, 
      RIKEN, Yokohama, Japan.
FAU - Nakamura, Yusuke
AU  - Nakamura Y
AD  - Laboratory of Molecular Medicine, Human Genome Center, The Institute of Medical 
      Science, University of Tokyo, Tokyo, Japan.
FAU - Chayama, Kazuaki
AU  - Chayama K
AD  - Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, 
      RIKEN, Hiroshima, Japan ; Department of Gastroenterology and Metabolism, Applied 
      Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, 
      Hiroshima, Japan ; Liver Research Project Center, Hiroshima University, 
      Hiroshima, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131220
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Asian People/*genetics
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease/*genetics
MH  - Genome-Wide Association Study
MH  - HLA-DQ beta-Chains/*genetics
MH  - Hepatitis C, Chronic/*genetics
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Logistic Models
MH  - Polymorphism, Single Nucleotide/genetics
PMC - PMC3871580
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/01/01 06:00
MHDA- 2014/10/14 06:00
PMCR- 2013/12/20
CRDT- 2013/12/31 06:00
PHST- 2013/09/19 00:00 [received]
PHST- 2013/11/20 00:00 [accepted]
PHST- 2013/12/31 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/10/14 06:00 [medline]
PHST- 2013/12/20 00:00 [pmc-release]
AID - PONE-D-13-38585 [pii]
AID - 10.1371/journal.pone.0084226 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 20;8(12):e84226. doi: 10.1371/journal.pone.0084226. 
      eCollection 2013.