PMID- 28812990
OWN - NLM
STAT- MEDLINE
DCOM- 20180425
LR  - 20221207
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 8
DP  - 2017 Aug 16
TI  - Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 
      are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese.
LID - 10.3390/ijms18081775 [doi]
LID - 1775
AB  - Human leukocyte antigen (HLA) class I ligands and Killer immunoglobulin-like 
      receptors (KIRs) regulate the cytolytic activity of natural killer (NK) cells and 
      certain T cells. We examined their genetic predisposition to disease 
      susceptibility and clinical phenotypes in Taiwanese ankylosing spondylitis (AS) 
      patients. KIR genotyping and Human Leucocyte Antigen C (HLA-C) sequencing were 
      performed in 653 Taiwanese AS patients and 952 healthy controls. KIR genotype 
      distributions and HLA-C allele frequencies were compared in patients and controls 
      and among patients with and without HLA-B27 positivity, early age onset and 
      spinal syndesmophytes. HLA-C alleles were functionally characterized using 3D 
      structural modelling with peptide simulation. This study discovered that the 
      HLA-C*12:02:02 allele (43.42% vs. 3.31%; p < 0.00001 odds ratio (OR), 16.88; 95% 
      confidence intervals (CI): 11.27-25.28) confers a strong risk for Taiwanese AS 
      development. The 3D modelling results identified four unique amino acid 
      polymorphisms, Ala73, Trp156, Arg219 and Met304, that may affect the function of 
      the HLA-C*12:02:02 allele. KIR2DL5 (p = 0.0047; p(FDR) = 0.0423) and the KIR Bx 
      haplotype (p = 0.0000275) were protective against Taiwanese AS, while KIR 2DS4/1D 
      (22 base pair truncated deletion; p = 0.0044; p(FDR) = 0.1998) appeared to be a 
      risk factor for it. KIR2DL5 combined with the HLA-C1/C2 heterozygous genotype 
      showed a protective effect (AS 5.97% vs. normal 11.66%; p = 0.002; p(FDR) = 
      0.0127, OR, 0.48 95% CI: 0.33-0.70); in contrast, KIR 2DS4/1D combined with the 
      HLA-C1C1 homozygous genotype (AS 45.33% vs. normal 35.92%; p = 0.002; p(FDR) = 
      0.0127, OR, 1.48 95% CI: 1.21-1.81) represented a risk factor for AS development. 
      Our data suggested that interactions between KIRs and their cognate HLA-C ligands 
      may contribute to the pathogenesis of AS.
FAU - Wang, Chin-Man
AU  - Wang CM
AD  - Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Taoyuan 33375, Taiwan. cmw1314@cgmh.org.tw.
FAU - Wang, Sheng-Hung
AU  - Wang SH
AD  - Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial 
      Hospital at Linkou, Taoyuan 33375, Taiwan. shawnwang@cgmh.org.tw.
FAU - Jan Wu, Yeong-Jian
AU  - Jan Wu YJ
AD  - Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang 
      Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin 
      St. Kuei-Shan, Taoyuan 33375, Taiwan. yjwu1962@adm.cgmh.org.tw.
FAU - Lin, Jing-Chi
AU  - Lin JC
AD  - Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang 
      Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin 
      St. Kuei-Shan, Taoyuan 33375, Taiwan. jingchilin@gmail.com.
FAU - Wu, Jianming
AU  - Wu J
AD  - Department of Veterinary and Biomedical Sciences, Department of Medicine, 
      University of Minnesota, St. Paul, MN 55108, USA. jmwu@umn.edu.
FAU - Chen, Ji-Yih
AU  - Chen JY
AD  - Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang 
      Gung Memorial Hospital, Chang Gung University College of Medicine, No. 5, Fu-Shin 
      St. Kuei-Shan, Taoyuan 33375, Taiwan. jychen31@adm.cgmh.org.tw.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
DEP - 20170816
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*12 antigen)
RN  - 0 (Receptors, KIR2DL5)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Alleles
MH  - Asian People
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - HLA-C Antigens/*genetics/immunology
MH  - Humans
MH  - Male
MH  - *Polymorphism, Genetic
MH  - Protein Domains
MH  - Receptors, KIR2DL5/*genetics/immunology
MH  - Spondylitis, Ankylosing/*genetics/immunology
MH  - Taiwan
PMC - PMC5578164
OTO - NOTNLM
OT  - ankylosing spondylitis
OT  - human leukocyte antigen C (HLA-C)
OT  - killer immunoglobulin-like receptor (KIR)
OT  - natural killer cell
COIS- The authors declare no conflict of interest.
EDAT- 2017/08/17 06:00
MHDA- 2018/04/26 06:00
PMCR- 2017/08/01
CRDT- 2017/08/17 06:00
PHST- 2017/07/26 00:00 [received]
PHST- 2017/08/11 00:00 [revised]
PHST- 2017/08/12 00:00 [accepted]
PHST- 2017/08/17 06:00 [entrez]
PHST- 2017/08/17 06:00 [pubmed]
PHST- 2018/04/26 06:00 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - ijms18081775 [pii]
AID - ijms-18-01775 [pii]
AID - 10.3390/ijms18081775 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Aug 16;18(8):1775. doi: 10.3390/ijms18081775.