Prioritization of PLEC and GRINA as Osteoarthritis Risk Genes Through the Identification and Characterization of Novel Methylation Quantitative Trait Loci.
Sarah J RiceMaria TselepiAntony K SorialGuillaume AubourgColin ShepherdDavid AlmarzaAndrew J SkeltonIoanna PangouDavid DeehanLouise N ReynardJohn LoughlinPublished in: Arthritis & rheumatology (Hoboken, N.J.) (2019)
PLEC encodes plectin, a cytoskeletal protein that maintains tissue integrity by regulating intracellular signaling in response to mechanical stimuli. GRINA encodes the ionotropic glutamate receptor TMBIM3 (transmembrane BAX inhibitor 1 motif-containing protein family member 3), which regulates cell survival. Based on our results, we hypothesize that in a joint predisposed to OA, expression of these genes alters in order to combat aberrant biomechanics, and that this is epigenetically regulated. However, carriage of the OA risk-conferring allele at this locus hinders this response and contributes to disease development.
Keyphrases
- genome wide
- knee osteoarthritis
- binding protein
- dna methylation
- poor prognosis
- protein protein
- high resolution
- transcription factor
- genome wide association study
- bioinformatics analysis
- gene expression
- genome wide identification
- reactive oxygen species
- oxidative stress
- signaling pathway
- long non coding rna
- long noncoding rna
- induced apoptosis