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. 2013 Jul;21(7):930-8.
doi: 10.1016/j.joca.2013.04.003. Epub 2013 Apr 18.

IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort

X Wu  1 , V Kondragunta, K S Kornman, H Y Wang, G W Duff, J B Renner, J M Jordan
Affiliations

IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort

X Wu et al. Osteoarthritis Cartilage. 2013 Jul.

Abstract

Objective: Within the interleukin-1 (IL-1) cytokine family, IL-1 receptor antagonist (IL1RN) gene variants have been associated with radiological severity of knee osteoarthritis (OA) in cross-sectional studies. The present study tested the relation between IL1RN gene variants and progression of knee OA assessed radiographically by change in Kellgren-Lawrence (KL) score over time.

Design: 1153 Caucasian adults (age range: 44-89) from the Johnson County Osteoarthritis Project were evaluated for unequivocal radiographic evidence of knee OA at baseline, defined as KL score ≥2, and were re-examined after 4-11 years for radiographic changes typical of OA progression. IL1RN gene variants were tested for association with OA progression and for potential interaction with body mass index (BMI). Other IL-1 gene variations were tested for association with OA progression as a secondary objective.

Results: Of 154 subjects with OA at baseline, 88 showed progression at follow-up. Seven IL1RN single nucleotide polymorphisms (SNPs) and one IL-1 receptor SNP were associated with progression. Four IL1RN haplotypes, each occurring in >5% of this population, showed different relationships with progression, including one (rs315931/rs4251961/rs2637988/rs3181052/rs1794066/rs419598/rs380092/rs579543/rs315952/rs9005/rs315943/rs1374281; ACAGATACTGCC) associated with increased progression [odds ratio (OR) 1.91 (95%CI 1.16-3.15); P = 0.012]. Haplotypes associated with progression by KL score were also associated with categorical change in joint space narrowing. BMI was associated with OA progression in subjects carrying a specific IL1RN haplotype, but not in subjects without that haplotype.

Conclusion: A significantly greater likelihood of radiological progression of knee OA was associated with a commonly occurring IL1RN haplotype that could be tagged by three IL1RN SNPs (rs419598, rs9005, rs315943). Interactions were also observed between IL1RN gene variants and BMI relative to OA progression. This suggests that IL1RN gene markers may be useful in stratifying patients for medical management and drug development.

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References

    1. Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58:15–25. - PubMed
    1. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58:26–35. - PMC - PubMed
    1. HCUP Nationwide Inpatient Sample (NIS) Healthcare Cost and Utilization Project (HCUP) Agency for Healthcare Research and Quality. Rockville MD: 1997-2009. www.hcup-us.ahrq.gov/nisoverview.jsp.
    1. Meulenbelt I, Min JL, Bos S, Riyazi N, Houwing-Duistermaat JJ, van der Wijk HJ, et al. Identification of DIO2 as a new susceptibility locus for symptomatic osteoarthritis. Hum Mol Genet. 2008;17:1867–75. - PubMed
    1. Zhai G, Hart DJ, Kato BS, MacGregor A, Spector TD. Genetic influence on the progression of radiographic knee osteoarthritis: a longitudinal twin study. Osteoarthritis Cartilage. 2007;15:222–5. - PubMed

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