Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene
Methods: Participants from the Genetics of OA and Lifestyle study were used for the discovery group (n = 1615). Genotype data for six SNPs selected to cover most variation in the TACR1 gene were used to test for an association with symptomatic OA. Replication analysis was performed using data from the Chingford 1000 Women Study, Hertfordshire Cohort Study, Tasmanian Older Adult Cohort Study and the Clearwater OA Study. In total, n = 1715 symptomatic OA and n = 735 asymptomatic OA individuals were analysed.
Results: Out of six SNPs tested in the TACR1 gene, one (rs11688000) showed a nominally significant association with a decreased risk of symptomatic OA in the discovery cohort. This was then replicated in four additional cohorts. After adjusting for age, gender, body mass index and radiographic severity, the G (minor) allele at rs11688000 was associated with a decreased risk of symptomatic OA compared to asymptomatic OA cases (p = 9.90 × 10-4 , OR = 0.79 95% 0.68-0.90 after meta-analysis).
Conclusions: This study supports a contribution from the TACR1 gene in human OA pain, supporting further investigation of this gene's function in OA.
Significance: This study contributes to the knowledge of the genetics of painful osteoarthritis, a condition which affects millions of individuals worldwide. Specifically, a contribution from the TACR1 gene to modulating pain sensitivity in osteoarthritis is suggested.
Funding
National Health & Medical Research Council
History
Publication title
European Journal of PainVolume
21Issue
7Pagination
1277-1284ISSN
1090-3801Department/School
Menzies Institute for Medical ResearchPublisher
W B Saunders Co LtdPlace of publication
32 Jamestown Rd, London, England, Nw1 7ByRights statement
Copyright 2017 European Pain Federation - EFIC. This is the peer reviewed version of the following article: Pain in knee osteoarthritis is associated with variation in the neurokinin 1/substance P receptor (TACR1) gene, which has been published in final form at http://dx.doi.org/10.1002/ejp.1027. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Repository Status
- Open