Journal
EUROPEAN JOURNAL OF HUMAN GENETICS
Volume 25, Issue 4, Pages 446-451Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2016.196
Keywords
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Funding
- University of Nottingham
- EULAR [108239]
- Arthritis Research UK Pain Centre [18769]
- Netherlands Society for Scientific Research (NWO) VIDI [917103521]
- Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- Municipality of Rotterdam
- ReumaFonds [LLP-11, COI-1] Funding Source: researchfish
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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 singlenucleotide 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= 1.29x10(-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.
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