Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee osteoarthritis (OA) in patients from the OAI
Main finding · Rapid progression of knee OA with G allele of rs12107036 (TP63) plus haplogroup UkResult — go to the resultOdds ratio 1.670 95% CI 1.031–2.706Authors' conclusion
This study demonstrates the existence of a mitonuclear epistasis in OA, providing new mechanisms by which nuclear and mitochondrial variation influence the susceptibility to develop different OA phenotypes.
Study context
- Population
- Subjects from the Osteoarthritis Initiative with follow-up of at least 48 months≥48-month follow-up
- Participants
- 1,095 subjects
- Exposure
- Simultaneous presence of the G allele of rs12107036 at TP63 and haplogroup Uk
- Outcome
- Rapid progression of knee OA
Methodological detailsgenetic association analysis, generalized estimating equations, adjusted for age, gender, BMI, contralateral knee OA, WOMAC pain, previous injury in target knee and mitochondrial deoxyribonucleic acid (mtDNA) variant m.16519C
- Genetic association analysis
- Generalized estimating equations
- Adjusted for age, gender, BMI, contralateral knee OA, WOMAC pain, previous injury in target knee and mtDNA variant m.16519C
Main finding
As reported in the abstract
Rapid progression of knee OA with G allele of rs12107036 (TP63) plus haplogroup Uk
Odds ratio
1.670
95% CI 1.031–2.706
adjusted p-value = 0.027
G allele of rs12107036 + haplogroup Uk
OR 1.670 (95% CI 1.031–2.706); adjusted p-value = 0.027
Observational data: associations, not effects.
Further findings
Population attributable fraction of rapid progressors, G allele of rs12107036 + haplogroup Uk
- Population attributable fraction (highest proportion of rapid progressors)
- 23.4%
- 95%CI: 7.89-38.9; p-value < 0.05
Model discrimination (AUC)
- AUC, cross-validation model
- 0.730
- AUC, predictive model
- 0.735
Original publication
Mitonuclear epistasis involving TP63 and haplogroup Uk: Risk of rapid progression of knee OA in patients from the OAI. Osteoarthritis Cartilage. Published 6 January 2024. doi:10.
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