title: Influence of CD94 and NKG2A variants on susceptibility to rheumatoid arthritis and efficacy of anti-TNF treatment.
abstract: OBJECTIVE
  The present study aimed to investigate relationships between the CD94 and NKG2A gene polymorphisms and the risk of rheumatoid arthritis (RA) development as well as their association with the response to anti-TNF therapy.
  
  
  METHODS
  A total of 284 patients with RA receiving anti-TNF therapy and 124 healthy subjects were enrolled to the study. Genotypings for CD94 (rs2302489) and NKG2A (rs7301582, rs2734440, rs2734414) polymorphisms were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays (TIB-MolBiol, Berlin, Germany). Clinical response was evaluated at 12th and 24th week after initiation of the therapy according to the EULAR response criteria.
  
  
  RESULTS
  The frequency of the CD94 AA genotype was significantly decreased in RA patients compared to controls (OR=0.44; P=0.016). The CD94 AA homozygotes were also more common among patients negative to anti-cyclic citrullinated peptide (anti-CCP) antibodies (OR=11.28; P=0.001) as compared to anti-CCP-positive patients and the presence of the CD94 allele A was associated with lack of anti-CCP antibodies (OR=5.00; P=0.0005). The CD94 rs2302489 TT genotype was over-represented in patients exhibiting worse EULAR response at 12th week (OR=3.33; P=0.017). Furthermore, the lack of response after 12 weeks was more frequent among patients carrying the NKG2A rs7301582C allele (OR=3.68; P=0.019) or the CC genotype (OR=3.58; P=0.035) in comparison to allele T or CT/TT genotypes, respectively.
  
  
  CONCLUSIONS
  These results indicate that CD94 and NKG2A polymorphisms may contribute to genetic susceptibility to RA or affect the response to anti-TNF therapy in patients of Caucasian origin.
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Iwaszko
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Świerkot
authors.affiliation: Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela, Bydgoszcz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kolossa
authors.affiliation: Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela, Bydgoszcz, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Jeka
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland. Electronic address: bogunia@iitd.pan.wroc.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics*; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate
keywords: Anti-TNF therapy; CD94 polymorphism; NKG2A polymorphism; Rheumatoid arthritis; TNF inhibitors