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Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis
  1. T Neogi1,
  2. A Soni2,
  3. S A Doherty3,
  4. L L Laslett4,
  5. R A Maciewicz5,
  6. D J Hart6,
  7. W Zhang3,
  8. K R Muir7,
  9. M Wheeler3,
  10. C Cooper2,8,
  11. T D Spector6,
  12. F Cicuttini9,
  13. G Jones4,
  14. M Nevitt10,
  15. Y Liu11,
  16. N K Arden2,8,
  17. M Doherty3,
  18. A M Valdes3,6
  1. 1 Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, USA
  2. 2 NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
  3. 3 Academic Rheumatology, Nottingham City Hospital, Nottingham, UK
  4. 4 Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia
  5. 5 Respiratory, Inflammation, Autoimmunity iMed, AstraZeneca AB, Mölndal, Sweden
  6. 6 Dept of Twin Research, King's College London, St Thomas' Hospital, London, UK
  7. 7 Institute of Population Health, University of Manchester, Manchester, UK
  8. 8 MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
  9. 9 Department of Epidemiology and Preventive Medicine, Monash University Medical School, Melbourne, Australia
  10. 10 Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA
  11. 11 Center for Human Genomics, Department of Epidemiology and Prevention, Division of Public Health Services, Wake Forest School of Medicine, North Carolina, USA
  1. Correspondence to Dr Ana M Valdes, Academic Rheumatology, University of Nottingham, Clinical Sciences Bld, Nottingham City Hospital, Nottingham NG5 1PB, UK; ana.valdes{at}

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There is extensive literature reporting discordance between the presence and severity of symptoms and the degree of radiographic structural osteoarthritis (OA).15 Genetic differences may account for some of this discordance. Indeed, certain genetic variants implicated in pain sensitivity have been shown to be significantly different between asymptomatic radiographic cases of OA and symptomatic cases.6–9

The catechol-O-methyltransferase, encoded by the COMT gene, is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters.10 Genetic variation at the COMT gene has been shown to result in differential pain sensitivity.10–12 Carriers of the Val158Met COMT variant have been reported to have a higher risk (OR=2.9, 95% CI 1.2 to 6.1) of hip pain as compared with carriers of the Val/Val genotype among those with hip OA.9 This result has not been replicated in independent cohorts, nor for OA in other joints.

We assessed whether the Met allele in the COMT gene is involved in increased risk of symptomatic knee OA in seven cohorts: five cohorts from the UK, …

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  • Contributors All authors contributed to the study design, data interpretation and the final manuscript. In addition, AMV and TN analysed and interpreted the data and prepared manuscript. AMV and TN supervised the study.

  • Funding Supported by EC-FP7 programme grant 200 800 TREAT-OA and by a EULAR project grant to AMV (grant 108239). Dr. Neogi was supported by NIH AR055127. AstraZeneca UK funded the GOAL study sample and data collection. The TwinsUK cohort is supported by the Wellcome Trust. The HCS is supported by the Medical Research Council (UK) and the Oxford NIHR Musculoskeletal Biomedical Research Unit. The Framingham Osteoarthritis Study was funded by NIH AR47785 and AG18393 and the NHLBI N01-HC-25195. The Health, Aging and Body Composition Study was supported by NIA contracts N01AG62101, N01AG62103 and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Centre for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. The Tasmanian Older Adult Cohort collection was funded by the National Health and Medical Research Council of Australia, Arthritis Foundation of Australia; Tasmanian Community Fund and a University of Tasmania Grant-Institutional Research Scheme.

  • Competing interests None.

  • Ethics approval The appropriate ethics committee approved the study protocol of each of the contributing cohort studies included.

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