Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/40117/ |
| _version_ | 1848795988782743552 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Warner, Sophie C. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:40:50Z |
| format | Article |
| id | nottingham-40117 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:40:50Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-401172020-05-04T18:31:53Z https://eprints.nottingham.ac.uk/40117/ 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. 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. Nature Publishing Group 2017-01-04 Article PeerReviewed 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 and Valdes, Ana M. (2017) 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 . ISSN 1476-5438 http://www.nature.com/ejhg/journal/vaop/ncurrent/full/ejhg2016196a.html 10.1038/ejhg.2016.196 10.1038/ejhg.2016.196 10.1038/ejhg.2016.196 |
| spellingShingle | 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. Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title | Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title_full | Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title_fullStr | Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title_full_unstemmed | Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title_short | Genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase C gene |
| title_sort | genome-wide association scan of neuropathic pain symptoms post total joint replacement highlights a variant in the protein-kinase c gene |
| url | https://eprints.nottingham.ac.uk/40117/ https://eprints.nottingham.ac.uk/40117/ https://eprints.nottingham.ac.uk/40117/ |