Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations.
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BACKGROUND: A lack of biomarkers that identify patients at risk for severe osteoarthritis (OA) complicates development of disease-modifying OA drugs. OBJECTIVE: To determine whether inflammatory genetic markers could stratify patients with knee OA into high and low risk for destructive disease. METHODS: Genotype associations with knee OA severity were assessed in two Caucasian populations. Fifteen single nucleotide polymorphisms (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) SNPs (rs419598, rs315952 and rs9005) predicted Kellgren-Lawrence scores independently in each population. One IL1RN haplotype was associated with lower odds of radiographic severity (OR=0.15; 95% CI 0.065 to 0.349; p<0.0001), greater joint space width 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 disease-modifying OA drug trials.
Genetic Predisposition to Disease
Interleukin 1 Receptor Antagonist Protein
Polymorphism, Single Nucleotide
Severity of Illness Index
Published Version (Please cite this version)10.1136/ard.2009.113043
Publication InfoAbramson, SB; Attur, M; Aziz, N; Bukowski, JF; Greenberg, J; Kornman, KS; ... Wang, H-Y (2010). Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations. Ann Rheum Dis, 69(5). pp. 856-861. 10.1136/ard.2009.113043. Retrieved from http://hdl.handle.net/10161/10879.
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Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis. Osteoarthritis is the most common form of joint disease in man and its incidence increases with age. It is a problem of increasing concern to the medical community due to the increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist, I endeavor to study this disease from bedside to bench. The work in this laboratory focuses on osteoarthritis and deals w