Next Article in Journal
lncRNA Gene Signatures for Prediction of Breast Cancer Intrinsic Subtypes and Prognosis
Next Article in Special Issue
Addendum: Iwaszko et al., Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis. Genes 2018, 9, 64
Previous Article in Journal
Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles in Synucleinopathies
Previous Article in Special Issue
The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection against Tuberculosis Disease in Argentina
Article Menu
Issue 2 (February) cover image

Export Article

Addendum published on 14 February 2018, see Genes 2018, 9(2), 94.

Open AccessArticle
Genes 2018, 9(2), 64;

Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis

Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wrocław, Poland
Department of Rheumatology and Internal Medicine, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela, Ujejskiego 75, 85-168 Bydgoszcz, Poland
Department of Internal, Occupational Diseases, Hypertension and Clinical Oncology, Wrocław Medical University, Borowska 213, 50-556 Wrocław, Poland
Author to whom correspondence should be addressed.
Received: 22 November 2017 / Revised: 16 January 2018 / Accepted: 18 January 2018 / Published: 25 January 2018
(This article belongs to the Special Issue DNA Variations in Evolution and Human Diseases)
Full-Text   |   PDF [262 KB, uploaded 15 February 2018]   |  


A natural killer group 2 member D (NKG2D) acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C > A). Clinical response was evaluated according to the European League against Rheumatism (EULAR) criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively). The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively). Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively). Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients. View Full-Text
Keywords: NKG2D polymorphism; anti-TNF therapy; TNF inhibitors NKG2D polymorphism; anti-TNF therapy; TNF inhibitors

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Iwaszko, M.; Świerkot, J.; Kolossa, K.; Jeka, S.; Wiland, P.; Bogunia-Kubik, K. Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis. Genes 2018, 9, 64.

Show more citation formats Show less citations formats

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

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top