PMID- 21998681
OWN - NLM
STAT- MEDLINE
DCOM- 20120213
LR  - 20220330
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 6
IP  - 10
DP  - 2011
TI  - KIR and HLA loci are associated with hepatocellular carcinoma development in 
      patients with hepatitis B virus infection: a case-control study.
PG  - e25682
LID - 10.1371/journal.pone.0025682 [doi]
LID - e25682
AB  - BACKGROUND: Natural killer (NK) cells activation has been reported to contribute 
      to inflammation and liver injury during hepatitis B virus (HBV) infection both in 
      transgenic mice and in patients. However, the role of NK cells in the process of 
      HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. 
      Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK 
      cell activation through recognition of specific human leukocyte antigen (HLA) 
      class I allotypes. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether KIR and 
      HLA genes could influence the risk of HBV-associated HCC development, 144 
      HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic 
      hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The 
      presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were 
      genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), 
      HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 
      bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found 
      associated with HCC incidence. When the combined effects of these three genetic 
      factors were evaluated, more risk factors were observed correlating with higher 
      odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors 
      we found have been reported to result in high NK cell functional potential by 
      previous studies, our observations suggest that NK cell activation may contribute 
      to HBV-associated HCC development. CONCLUSIONS/SIGNIFICANCE: In conclusion, this 
      study has identified significant associations that suggest an important role for 
      NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC 
      surveillance and has implications for novel personalized therapy strategy 
      development aiming at HCC prevention in HBV-infected patients.
FAU - Pan, Ning
AU  - Pan N
AD  - Department of Immunology and pathogen biology, Southeast University Medical 
      School, Nanjing, Jiangsu Province, China.
FAU - Jiang, Wei
AU  - Jiang W
FAU - Sun, Hang
AU  - Sun H
FAU - Miao, Fengqin
AU  - Miao F
FAU - Qiu, Jie
AU  - Qiu J
FAU - Jin, Hui
AU  - Jin H
FAU - Xu, Jinhuan
AU  - Xu J
FAU - Shi, Qian
AU  - Shi Q
FAU - Xie, Wei
AU  - Xie W
FAU - Zhang, Jianqiong
AU  - Zhang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111005
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (HLA Antigens)
RN  - 0 (Receptors, KIR)
SB  - IM
MH  - Adult
MH  - Carcinoma, Hepatocellular/complications/*genetics/virology
MH  - Case-Control Studies
MH  - Disease Progression
MH  - Female
MH  - Gene Dosage/genetics
MH  - Genetic Loci/*genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - HLA Antigens/*genetics
MH  - Hepatitis B/*complications
MH  - Humans
MH  - Killer Cells, Natural/metabolism
MH  - Liver Neoplasms/complications/*genetics/virology
MH  - Male
MH  - Middle Aged
MH  - Receptors, KIR/*genetics
PMC - PMC3187788
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2011/10/15 06:00
MHDA- 2012/02/14 06:00
PMCR- 2011/10/05
CRDT- 2011/10/15 06:00
PHST- 2011/05/25 00:00 [received]
PHST- 2011/09/08 00:00 [accepted]
PHST- 2011/10/15 06:00 [entrez]
PHST- 2011/10/15 06:00 [pubmed]
PHST- 2012/02/14 06:00 [medline]
PHST- 2011/10/05 00:00 [pmc-release]
AID - PONE-D-11-09404 [pii]
AID - 10.1371/journal.pone.0025682 [doi]
PST - ppublish
SO  - PLoS One. 2011;6(10):e25682. doi: 10.1371/journal.pone.0025682. Epub 2011 Oct 5.