PMID- 24349500
OWN - NLM
STAT- MEDLINE
DCOM- 20140929
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - KIR, HLA, and IL28B variant predict response to antiviral therapy in genotype 1 
      chronic hepatitis C patients in Japan.
PG  - e83381
LID - 10.1371/journal.pone.0083381 [doi]
LID - e83381
AB  - Natural killer cell responses play a crucial role in virus clearance by the 
      innate immune system. Although the killer immunoglobulin-like receptor (KIR) in 
      combination with its cognate human leukocyte antigen (HLA) ligand, especially 
      KIR2DL3-HLA-C1, is associated with both treatment-induced and spontaneous 
      clearance of hepatitis C virus (HCV) infection in Caucasians, these innate 
      immunity genes have not been fully clarified in Japanese patients. We therefore 
      investigated 16 KIR genotypes along with HLA-B and -C ligands and a genetic 
      variant of interleukin (IL) 28B (rs8099917) in 115 chronic hepatitis C genotype 1 
      patients who underwent pegylated-interferon-alpha2b (PEG-IFN) and ribavirin therapy. 
      HLA-Bw4 was significantly associated with a sustained virological response (SVR) 
      to treatment (P = 0.017; odds ratio [OR] = 2.50, ), as was the centromeric A/A 
      haplotype of KIR (P = 0.015; OR 3.37). In contrast, SVR rates were significantly 
      decreased in patients with KIR2DL2 or KIR2DS2 (P = 0.015; OR = 0.30, and P = 
      0.025; OR = 0.32, respectively). Multivariate logistic regression analysis 
      subsequently identified the IL28B TT genotype (P = 0.00009; OR = 6.87, 95% 
      confidence interval [CI] = 2.62 - 18.01), KIR2DL2/HLA-C1 (P = 0.014; OR = 0.24, 
      95% CI = 0.08 - 0.75), KIR3DL1/HLA-Bw4 (P = 0.008, OR = 3.32, 95% CI = 1.37 - 
      8.05), and white blood cell count at baseline (P = 0.009; OR = 3.32, 95% CI = 
      1.35 - 8.16) as independent predictive factors of an SVR. We observed a 
      significant association between the combination of IL28B TT genotype and 
      KIR3DL1-HLA-Bw4 in responders (P = 0.0019), whereas IL28B TT along with 
      KIR2DL2-HLA-C1 was related to a non-response (P = 0.0067). In conclusion, 
      combinations of KIR3DL1/HLA-Bw4, KIR2DL2/HLA-C1, and a genetic variant of the 
      IL28B gene are predictive of the response to PEG-IFN and ribavirin therapy in 
      Japanese patients infected with genotype 1b HCV.
FAU - Nozawa, Yuichi
AU  - Nozawa Y
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Umemura, Takeji
AU  - Umemura T
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Joshita, Satoru
AU  - Joshita S
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Katsuyama, Yoshihiko
AU  - Katsuyama Y
AD  - Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
FAU - Shibata, Soichiro
AU  - Shibata S
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Kimura, Takefumi
AU  - Kimura T
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Morita, Susumu
AU  - Morita S
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Komatsu, Michiharu
AU  - Komatsu M
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Matsumoto, Akihiro
AU  - Matsumoto A
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Tanaka, Eiji
AU  - Tanaka E
AD  - Division of Hepatology and Gastroenterology, Department of Medicine, Shinshu 
      University School of Medicine, Matsumoto, Japan.
FAU - Ota, Masao
AU  - Ota M
AD  - Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, 
      Japan.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131212
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Antiviral Agents)
RN  - 0 (HLA Antigens)
RN  - 0 (interferon-lambda, human)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukins)
RN  - 0 (Receptors, KIR)
RN  - 0 (Recombinant Proteins)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 9008-11-1 (Interferons)
RN  - Q46947FE7K (peginterferon alfa-2a)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antiviral Agents/*administration & dosage
MH  - Female
MH  - HLA Antigens/*genetics/immunology
MH  - Hepatitis C, Chronic/*drug therapy/*genetics/immunology
MH  - Humans
MH  - Interferon-alpha/*administration & dosage
MH  - Interferons
MH  - Interleukins/*genetics/immunology
MH  - Male
MH  - Middle Aged
MH  - Polyethylene Glycols/*administration & dosage
MH  - Receptors, KIR/*genetics/immunology
MH  - Recombinant Proteins/administration & dosage
PMC - PMC3861489
COIS- Competing Interests: MSD partly funded this study. There are no patents, products 
      in development or marketed products to declare. This does not alter the authors' 
      adherence to all the PLOS ONE policies on sharing data and materials.
EDAT- 2013/12/19 06:00
MHDA- 2014/09/30 06:00
PMCR- 2013/12/12
CRDT- 2013/12/19 06:00
PHST- 2013/09/03 00:00 [received]
PHST- 2013/11/02 00:00 [accepted]
PHST- 2013/12/19 06:00 [entrez]
PHST- 2013/12/19 06:00 [pubmed]
PHST- 2014/09/30 06:00 [medline]
PHST- 2013/12/12 00:00 [pmc-release]
AID - PONE-D-13-36203 [pii]
AID - 10.1371/journal.pone.0083381 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 12;8(12):e83381. doi: 10.1371/journal.pone.0083381. 
      eCollection 2013.