Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Association of Osteoarthritis-Related Knee Pain with a Functional Polymorphism of the Catechol-O-Methyltransferase Gene

Neogi1,  T., Wang1,  K., Kammerer2,  C., Ferrell2,  R., Garcia3,  M., Kwoh2,  C. K., Harris3,  T.

BUSM, Boston, MA
UPittsburgh, Pittsburgh, PA
NIA, Bethesda, MD
UofTennessee, Memphis, TN
UCSF, San Francisco, CA


Pain related to musculoskeletal complaints is the most common reason for outpatient visits, with knee being the primary site of pain, yet little is understood about pain in musculoskeletal conditions. It is well known that in osteoarthritis (OA) there are individuals in whom their symptoms appear to be discordant with the degree of disease on radiographs. Some of this between-person variability may be related to genetic factors that contribute to the experience of pain. Recently, a functional polymorphism of the catechol-O-methyltransferase (COMT) gene has been reported to be associated with pain sensitivity, as well as hip-OA related pain. We evaluated the association of a functional polymorphism of COMT with knee pain, particularly OA-related knee pain, among well-functioning older adults.


Health, Aging and Body Composition Study is a longitudinal study of well-functioning elders. Genotypes of the Val158Met (rs4680) COMT polymorphism were determined by the TaqMan procedure (Applied Biosystems, Inc), with 5% blind duplicate procedures, and quality control with direct sequencing of a subset of samples. At baseline, participants were asked whether they had knee pain on most days: 1) of a month in the past 12 months; 2) of the past 30 days; or 3) moderate or worse pain with any activity by WOMAC. Those with knee pain and selected controls had knee x-rays. Presence of radiographic OA was defined as Kellgren and Lawrence grade >=2 or presence of patellofemoral OA. We evaluated the association of having >=1 methionine (Met) allele of the rs4680 SNP (dominant mode of inheritance) with presence of knee pain on most days of the month in the past 12 months, and of the past 30 days using logistic regression, adjusting for age, sex, BMI, depressive symptoms (CES-D), race and presence of radiographic OA.


There were 1128 individuals who had x-rays taken (mean age 74.6±2.9, 58.5% female, mean BMI 27.7±5 kg/m2, 66% with >=1 Met allele, 50% with knee OA). Having >=1 Met allele in the rs4680 SNP was associated with presence of knee pain on most days of a month of the past 12 months (adj OR 1.44, 95% CI 1.09–1.91), as well as pain on most days of the past 30 days (adj OR 1.43 95% CI 1.08–1.89), with effects attenuated after adjustment for race due to allele frequency differences (past 12 months: adj OR 1.31 (0.98–1.74); past 30 days adj OR 1.26 (0.95–1.68)), but with no effect measure modification by race noted (similar effect estimates in both races). Similar effects were noted for pain among those with knee OA ((past 12 months: adj OR 1.29 (0.84–1.99), past 30 days: adj OR 1.27 (0.83–1.95)).


The Val158Met functional polymorphism of COMT was associated with knee pain. This COMT polymorphism may explain in part the observed variation in pain and structural abnormalities noted in persons with OA, and needs to be replicated in larger samples.

To cite this abstract, please use the following information:
Neogi, T., Wang, K., Kammerer, C., Ferrell, R., Garcia, M., Kwoh, C. K., et al; Association of Osteoarthritis-Related Knee Pain with a Functional Polymorphism of the Catechol-O-Methyltransferase Gene [abstract]. Arthritis Rheum 2009;60 Suppl 10 :631
DOI: 10.1002/art.25711

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