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Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene

Warner, Sophie C.; van Meurs, Joyce B.J.; Schiphof, Dieuwke; Bierma-Zeinstra, Sita M.; Hofman, Albert; Uitterlinden, Andre G.; Richardson, Helen; Jenkins, Wendy; Doherty, Michael; Valdes, Ana M.

Authors

Sophie C. Warner

Joyce B.J. van Meurs

Dieuwke Schiphof

Sita M. Bierma-Zeinstra

Albert Hofman

Andre G. Uitterlinden

Helen Richardson

Wendy Jenkins

Michael Doherty

Ana M. Valdes



Abstract

Neuropathic pain-like joint symptoms (NP) are seen in a proportion of individuals diagnosed with osteoarthritis (OA) and post total joint replacement (TJR). In this study, we performed a genome-wide association study (GWAS) using NP as defined by the painDETECT questionnaire (score >12 indicating possible NP) in 613 post-TJR participants recruited from Nottinghamshire (UK). The prevalence of possible NP was 17.8%. The top four hits from the GWAS and two other biologically relevant single-nucleotide polymorphisms (SNPs) were replicated in individuals with OA and post TJR from an independent study in the same area (N=908) and in individuals from the Rotterdam Study (N=212). Three of these SNPs showed effect sizes in the same direction as in the GWAS results in both replication cohorts. The strongest association upon meta-analysis of a recessive model was for the variant allele in rs887797 mapping to the protein kinase C alpha (PRKCA) gene odds ratio (OR)possNP=2.41 (95% CI 1.74–3.34, P=1.29 × 10−7). This SNP has been found to be associated with multiple sclerosis and encodes a functional variant affecting splicing and expression of the PRKCA gene. The PRKCA gene has been associated with long-term potentiation, synaptic plasticity, chronic pain and memory in the literature, making this a biologically relevant finding.

Citation

Warner, S. C., van Meurs, J. B., Schiphof, D., Bierma-Zeinstra, S. M., Hofman, A., Uitterlinden, A. G., …Valdes, A. M. (in press). Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene. European Journal of Human Genetics, https://doi.org/10.1038/ejhg.2016.196

Journal Article Type Article
Acceptance Date Dec 6, 2016
Online Publication Date Jan 4, 2017
Deposit Date Jan 26, 2017
Publicly Available Date Jan 26, 2017
Journal European Journal of Human Genetics
Print ISSN 1018-4813
Electronic ISSN 1476-5438
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1038/ejhg.2016.196
Public URL http://eprints.nottingham.ac.uk/id/eprint/40117
Publisher URL http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2016196a.html
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf

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Warner et al EJHG final version of paper.pdf (484 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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