Background The relationship between ADAMTS genes and osteoarthritis (OA) may be crucial since these genes and their products may be used as biomarkers for prognosis and treatment of OA.

Objectives To determine the role of cytosine-adenine (CA) micro-satellite repeat sequence of ADAMTS9 gene on the development and progression of OA.

Methods Inclusion criteria for participants were ages 40 to 75 years, primary knee OA based on ACR knee OA criteria. Exclusion criteria included inflammatory rheumatic diseases, intraarticular injections, previous knee surgery, neurological or neuromuscular diseases, malignancies and secondary forms of knee OA. Patients were stratified into 2 groups using the K-L stages, based on radiologic severity as follows: Group 1: Stages 0 (no findings of OA including controls), Stages 1, 2 (mild OA) and Group 2: Stages 3,4 (moderately severe and severe OA).

Results A total of 110 participants were enrolled. No significant differences were detected between group 1 and 2 in respect to sex, occupation, physical activity, smoking status, family history, ESR and CRP. When the length of CA repeat in ADAMTS9 gene was compared between group 1 and 2, for the right knee AUC of ROC curve was statistically significant (p=0.021). For the right knee, the 20-CA repeats was found to be statistically significant for differentiating groups 1 and 2 (p=0.02). For CA repeat length of ≥20, sensitivity was 39%, specificity was 81.2%, positive predictive value was 55.2%, negative predictive value was 69.1%, and diagnostic accuracy was 65.4%. Among all the risk factors included, age was the most significant risk factor, followed by ≥20 CA repeat and BMI. When corrected for the other risk factors, every 10-year increase in age was found to result in 2.5 fold increase in the probability of progression of OA to stages 3 and 4 (p=0.003). CA repeat length of ≥20 showed a 6.1 fold increase in probability for having OA at stage 3 or 4 compared to those of CA repeat length of <20 (p=0.004). Every 5 kg/m² increase in BMI caused a 2.2 fold increase in the probability of having OA at stages 3 or 4 (p=0.022).

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Figure 1.

The sensitivity and specifity (ROC curve) based on the length of CA repeat in differentiating between group 1 (K-L stages 0, 1, 2) and group 2 (K-L stages 3, 4) of the right knee.

Conclusions When all risk factors are considered, older age, CA repeat of ≥20, and higher BMI are risk factors for progression into stage 3 and 4 in OA. The CA repeat length of ≥20 has a 6 fold increase in probability for having radiologically severe OA. This suggests that, ADAMTS9 gene CA repeat polymorphism may be used to determine the prognosis for OA radiologic progression. This could be highlighted further in future studies by studying CA repeat polymorphism in ADAMTS9 gene in larger sample size.

References

1. Jones GC, Riley GP. ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular matrix turnover and arthritis. Arthritis research & therapy. 2005;7(4):160-9.

2. Nagase H, Kashiwagi M. Aggrecanases and cartilage matrix degradation. Arthritis Res Ther. 2003;5(2):94-103.

3. Tang BL. ADAMTS: a novel family of extracellular matrix proteases. The international journal of biochemistry & cell biology. 2001;33(1):33-44.

Disclosure of Interest : None declared

DOI 10.1136/annrheumdis-2014-eular.2280