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The (−765 G→C) promoter variant of the COX-2/PTGS2 gene is associated with a lower risk for end-stage hip and knee osteoarthritis
  1. E M Schneider1,
  2. W Du1,
  3. J Fiedler2,
  4. J Högel3,
  5. K P Günther4,
  6. H Brenner5,
  7. R E Brenner2
  1. 1Division for Experimental Anaesthesiology, Department of Anaesthesiology, University Hospital Ulm, Ulm, Germany
  2. 2Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University Hospital Ulm, Ulm, Germany
  3. 3Institute of Human Genetics, University of Ulm, Ulm, Germany
  4. 4Department of Orthopedic Surgery, University Hospital Dresden, Dresden, Germany
  5. 5Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
  1. Correspondence to Professor Dr R E Brenner, Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University Hospital Ulm, Oberer Eselsberg 45, 89081 Ulm, Germany; rolf.brenner{at}uni-ulm.de

Abstract

Background Functional polymorphisms in genes of proinflammatory signalling cascades may contribute to the genetic risk of osteoarthritis (OA).

Objective To examine a possible association between end-stage OA of the hip and knee joint and a known single nucleotide polymorphism (SNP) of the COX-2 gene promoter.

Methods The SNP −765 G→C (rs20417) of the COX-2 gene promoter was genotyped by pyrosequencing in 531 (320 women/211 men) patients with OA from the Ulm Osteoarthritis Study and 400 (200 women/200 men) regional controls from the south-west of Germany.

Results In the whole study population the C allele was associated with a lower risk (per allele OR 0.57; 95% CI 0.43 to 0.75, p<0.0001) and the G allele with a higher risk for end-stage OA. Analysis of subgroups confirmed this result for primary, bilateral, hip and knee OA.

Conclusion The promoter polymorphism rs20417 of the COX-2 gene contributes to the genetic risk for end-stage hip and knee OA.

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Footnotes

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Local Ethics Committee of the University of Ulm, Germany, and the consent of the patients.

  • Provenance and peer review Not commissioned; externally peer reviewed.