Contribution of the COMT Val158Met variant to symptomatic knee osteoarthritis

There is extensive literature reporting discordance between the presence and severity of symptoms and the degree of radiographic structural osteoarthritis (OA). 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.

The catechol-O-methyltransferase, encoded by the COMT gene, is a major degrading enzyme in the metabolic pathways of catecholaminergic neurotransmitters. Genetic variation at the COMT gene has been shown to result in differential pain sensitivity. 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. 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 two from the USA were included (table 1). Assembly of the cohorts was approved by the local research ethics committees and all study participants gave fully informed consent to participate in genetic studies.