Next Article in Journal
The Retinoblastoma (RB) Tumor Suppressor: Pushing Back against Genome Instability on Multiple Fronts
Next Article in Special Issue
Human Leukocyte Antigen Class I and Class II Polymorphisms and Serum Cytokine Profiles in Cervical Cancer
Previous Article in Journal
Epigenome Aberrations: Emerging Driving Factors of the Clear Cell Renal Cell Carcinoma
Previous Article in Special Issue
HLA-G 3′UTR Polymorphisms Predict Drug-Induced G3-4 Toxicity Related to Folinic Acid/5-Fluorouracil/Oxaliplatin (FOLFOX4) Chemotherapy in Non-Metastatic Colorectal Cancer
Article

Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese

1
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan 33375, Taiwan
2
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan 33375, Taiwan
3
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
4
Department of Veterinary and Biomedical Sciences, Department of Medicine, University of Minnesota, St. Paul, MN 55108, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(8), 1775; https://doi.org/10.3390/ijms18081775
Received: 26 July 2017 / Revised: 11 August 2017 / Accepted: 12 August 2017 / Published: 16 August 2017
(This article belongs to the Special Issue Major Histocompatibility Complex)
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; pFDR = 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; pFDR = 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; pFDR = 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; pFDR = 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. View Full-Text
Keywords: ankylosing spondylitis; natural killer cell; human leukocyte antigen C (HLA-C); killer immunoglobulin-like receptor (KIR) ankylosing spondylitis; natural killer cell; human leukocyte antigen C (HLA-C); killer immunoglobulin-like receptor (KIR)
Show Figures

Graphical abstract

MDPI and ACS Style

Wang, C.-M.; Wang, S.-H.; Jan Wu, Y.-J.; Lin, J.-C.; Wu, J.; Chen, J.-Y. Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese. Int. J. Mol. Sci. 2017, 18, 1775. https://doi.org/10.3390/ijms18081775

AMA Style

Wang C-M, Wang S-H, Jan Wu Y-J, Lin J-C, Wu J, Chen J-Y. Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese. International Journal of Molecular Sciences. 2017; 18(8):1775. https://doi.org/10.3390/ijms18081775

Chicago/Turabian Style

Wang, Chin-Man, Sheng-Hung Wang, Yeong-Jian Jan Wu, Jing-Chi Lin, Jianming Wu, and Ji-Yih Chen. 2017. "Human Leukocyte Antigen C*12:02:02 and Killer Immunoglobulin-Like Receptor 2DL5 are Distinctly Associated with Ankylosing Spondylitis in the Taiwanese" International Journal of Molecular Sciences 18, no. 8: 1775. https://doi.org/10.3390/ijms18081775

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop