Specific isoforms of the ubiquitin ligase gene WWP2 are targets of osteoarthritis genetic risk via a differentially methylated DNA sequence
Authors' conclusion
As far as we are aware, this is the first experimental demonstration of an OA association signal targeting specific transcript isoforms of a gene.
Study context
- Population
- Adult osteoarthritis (OA) (arthroplasty) and foetal cartilage; OA risk marked by single nucleotide polymorphism (SNP) rs34,195,470 (A > G) in WWP2
- Comparison
- OA cartilage vs Foetal cartilage
- Outcome
- rs34195470 mQTL (genotype-associated differential DNAm at 16 CpGs), CpG regulatory activity and effect of epigenetic editing on WWP2 isoform and miR-140 expression
Methodological detailsfunctional fine-mapping, reporter gene assay, epigenetic editing, in silico analysis
- Functional fine-mapping
- Reporter gene assay
- Epigenetic editing
- In silico analysis
Main finding
As reported in the abstract
rs34195470 genotype associates with differential methylation in OA cartilage, forming an methylation quantitative trait locus (mQTL) (CpGs)
14 of the 16
mQTL less pronounced in foetal cartilage (CpGs)
5 of 16
Original publication
Specific isoforms of the ubiquitin ligase gene WWP2 are targets of osteoarthritis genetic risk via a differentially methylated DNA sequence. Arthritis Res Ther. Published 3 April 2024. doi:10.
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