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Clinical and epidemiological research
Concise report
Genetic contribution to radiographic severity in osteoarthritis of the knee
  1. Ana M Valdes1,
  2. Sally Doherty2,
  3. Kenneth R Muir3,
  4. Weiya Zhang4,
  5. Rose A Maciewicz5,
  6. Margaret Wheeler2,
  7. Nigel Arden6,
  8. Cyrus Cooper7,
  9. M Doherty2
  1. 1Twin Research Unit, Kings College London, London, UK
  2. 2Academic Rheumatology, University of Nottingham, Nottingham, UK
  3. 3Health Sciences Research Institute, University of Warwick, Warwick, UK
  4. 4Academic Rheumatology, Nottingham University, Nottingham, UK
  5. 5Respiratory & Inflammation iMed, AstraZeneca, Loughborough, UK
  6. 6University of Southampton, Southampton, UK
  7. 7MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK
  1. Correspondence to Dr Ana M Valdes, Kings College London, Twin Research Unit, St Thomas Hospital, Lambeth Palace Rd, London SE1 7EH, UK; ana.valdes{at}kcl.ac.uk

Abstract

Objective Knee osteoarthritis (OA) has a significant genetic component. The authors have assessed the role of three variants reported to influence risk of knee OA with p<5×10–8 in determining patellofemoral and tibiofemoral Kellgren Lawrence (K/L) grade in knee OA cases.

Methods 3474 knee OA cases with sky-line and weight-bearing antero-posterior x-rays of the knee were selected based on the presentation of K/L grade ≥2 at either the tibiofemoral or patellofemoral compartments for one or both knees. Patients belonging to three UK cohorts, were genotyped for rs143383, rs4730250 and rs11842874 mapping to the GDF5, COG5 and MCF2L genes, respectively. The association between tibiofemoral K/L grade and patellofemoral K/L grade was assessed after adjusting for age, gender and body mass index.

Results No significant association was found between the rs4730250 and radiographic severity. The rs11842874 mapping to MCF2L was found to be nominally significantly associated with patellofemoral K/L grade as a quantitative trait (p=0.027) but not as a binary trait. The GDF5 single nucleotide polymorphism rs143383 was associated with tibiofemoral K/L grade (β=0.05 (95% CI 0.02 to 0.08) p=0.0011).

Conclusions Our data indicate that within individuals affected by radiographic knee OA, OAGDF5 has a modest but significant effect on radiographic severity after adjustment for the major risk factors.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/3.0/ and http://creativecommons.org/licenses/by-nc/3.0/legalcode

https://doi.org/10.1136/annrheumdis-2012-201382

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    Footnotes

    • Funding This study was supported by the European Commission Framework Programme 7.

    • Competing interests RAM is an employee and owns stock of Astra Zeneca plc. All other authors declare no conflict of interest.

    • Patient Consent Obtained.

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