Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Interleukin-1 Receptor Antagonist (IL-1RN) Gene Variations Predict the Severity and Progression of Knee Osteoarthritis.

Attur8,  Mukundan, Oh7,  Cheongun, Krasnokutsky6,  Svetlana, Samuels5,  Jonathan, Rybak9,  Leon, Bencardino9,  Jenny, Greenberg1,  Jeffrey D.

Millburn, NJ
Duke University Medical Center, Durham, NC
Hospital for Joint Dis/NYU, New York, NY
Interleukin Genetics
New York University Hospital for Joint Disease, New York, NY
NYU Hospital for Joint Disease, New York, NY
NYU-Hospital for Joint Diseases
NYU-Hospital for Joint Diseases, New York, NY
NYU-Hospital for Joint Diseases Radiology Dept.

Purpose:

We have previously shown that carriage of an IL1RN haplotype (CTA) was associated with substantially lower odds of radiographic severity (KL score, joint space width [JSW]) (Ann Rheum Dis. 2010). In this 24 month prospective study we assessed whether IL1-RN haplotypes predicted disease progression in patients with symptomatic knee OA.

Methods:

Ninety-seven (N=97) patients from NYUHJD who met ACR criteria for symptomatic knee OA were genotyped for single nucleotide polymorphisms (SNPs) in the IL-1b and IL-1RN genes. Standardized fixed-flexion radiographs were taken on all patients at baseline and 24 months. Radiographic progression of signal (more painful) knee OA was determined by change in JSW over 24 months. To account for variations in baseline JSW, we defined progression as greater than 30% joint space narrowing (JSN) of the diseased compartment over 24 months, rather than in change in absolute JSW in millimeters.

Results:

Decreases in JSW ranged from zero to 3.7 mm over the 24 months; 19 of 97 patients exhibited > 30% JSN.

Patients with the IL-1RN (rs419598/rs315952/9005) TTG haplotype exhibited increased radiographic knee OA severity at baseline compared to those without TTG (p<0.08). These TTG patients exhibited increased risk for radiographic progression at 24 months that approached significance based on >=30% JSN [OR = 2.85; 95%CI=0.68–11.67; p<0.15]. In contrast, OA patients with IL-1RN CTA haplotype showed decreased risk for JSN over 24 months in the signal knee [OR= 0.33; 95%CI=0.170–1.014; p<0.05]. Differences in reported VAS pain between the CTA and TTG group were significant at 24 months (p< 0.01), indicating that while these patients were not distinguishable by radiograph or symptoms at onset, IL1RN haplotype predicted symptomatic differences at two years. Finally, the TTG haplotype group of patients expressed relatively increased IL-1b gene expression [15.683 ± 9.407 (p<0.0001)] as assessed by TaqMan QPCR in peripheral blood leukocytes. The TTG patients also exhibited decreased sIL-1Ra [283.64 ± 36.4 pg/ml (p<0.001) in plasma samples compared to IL-1RN CTA haplotype protective groups [IL-1b (fold change), 5.444 ± 10.083; sIL-1Ra, 370.35 ± 43.3pg/ml] of patients respectively.

Conclusion:

IL-1RN gene family polymorphisms, which appear to affect host production of IL-1Ra, merit evaluation as biomarkers that predict the risk of progression in patients with symptomatic knee OA.

To cite this abstract, please use the following information:
Attur, Mukundan, Oh, Cheongun, Krasnokutsky, Svetlana, Samuels, Jonathan, Rybak, Leon, Bencardino, Jenny, et al; Interleukin-1 Receptor Antagonist (IL-1RN) Gene Variations Predict the Severity and Progression of Knee Osteoarthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :707
DOI: 10.1002/art.28475

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