Objective: The lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs (DMOADs) This study determined whether inflammatory genetic markers could stratify knee OA patients into high and low risk for destructive disease.
Methods: Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen SNPs in six inflammatory genes were evaluated for association with radiographic severity and with synovial fluid mediators in a subset of the patients.
Results: Interleukin-1-receptor antagonist (IL1RN) single-nucleotide polymorphisms (rs419598; rs315952; and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR 0.16; 95% CI 0.06-0.40), greater joint space width (JSW; p=0.0038), and lower synovial fluid cytokine levels. Carriage of the IL1RN haplotype influenced the age relationship with severity.
Conclusion: IL1RN Polymorphisms reproducibly contribute to disease severity in knee OA and may be useful biomarkers for patient selection in DMOAD trials.