Article Text

other Versions

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. 1Clinical Epidemiology Research and Training Unit, Boston University School of Medicine, Boston, MA, USA
  2. 2NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK
  3. 3Academic Rheumatology, Nottingham City Hospital, Nottingham, UK
  4. 4Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia
  5. 5Respiratory, Inflammation, Autoimmunity iMed, AstraZeneca AB, Mölndal, Sweden
  6. 6Dept of Twin Research, King's College London, St Thomas' Hospital, London, UK
  7. 7Institute of Population Health, University of Manchester, Manchester, UK
  8. 8MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK
  9. 9Department of Epidemiology and Preventive Medicine, Monash University Medical School, Melbourne, Australia
  10. 10Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, CA, USA
  11. 11Center 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}

Statistics from

There is extensive literature reporting discordance between the presence and severity of symptoms and the degree of radiographic structural osteoarthritis (OA).1–5 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, one from Australia and …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.