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Clinical and epidemiological research
Extended report
Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations
  1. Mukundan Attur1,
  2. Hwa-Ying Wang2,
  3. Virginia Byers Kraus3,
  4. Jack F Bukowski2,4,
  5. Nazneen Aziz2,
  6. Svetlana Krasnokutsky1,
  7. Jonathan Samuels1,
  8. Jeffrey Greenberg1,
  9. Gary McDaniel3,
  10. Steven B Abramson1,
  11. Kenneth S Kornman2
  1. 1New York University Hospital for Joint Diseases, New York, USA
  2. 2Interleukin Genetics, Waltham, Massachusetts, USA
  3. 3Duke University Medical Center, Durham, North Carolina, USA
  4. 4Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Steven B Abramson, Division of Rheumatology, 301E, 17th Street Suite 1410, NYU Hospital for Joint Diseases, New York, NY 10003, USA; stevenb.abramson{at}nyumc.org

Abstract

Background A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs.

Objective To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease.

Methods Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (SNPs) in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients.

Results Interleukin 1 receptor antagonist (IL1RN) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren–Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity.

Conclusion IL1RN polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in disease-modifying OA drug trials.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

https://doi.org/10.1136/ard.2009.113043

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    Footnotes

    • Funding This study was funded in part by the following grants: grant from Interleukin Genetics to NYUHJD; NIH grant: RO1 AR052873-01 to NYUHJD; NIH grant: U01 AR050898 to Duke University.

    • Competing interests When the research was conducted JFB, NA and KSK were full-time employees and H-YW was a part-time consultant for Interleukin Genetics.

    • Patient consent Obtained.

    • Ethics approval This study was conducted with the approval of the NYU institutional review board.

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