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.
Novel Biomarkers of Knee Osteoarthritis Identified Using a Non-Targeted Metabolomic Approach.
Zhai, Guangju, Suhre, Karsten, Hart, Deborah, Gieger, Christian, Soranzo, Nicole, Spector, Tim D.
There is a pressing need to develop reliable molecular biomarkers that can inform on the process of joint destruction in osteoarthritis (OA). Such biomarkers could aid in drug development by identifying fast progressors and early response to therapy. Recent advance in metabolomics (the quantitative analysis of all metabolites present within a biological sample) has opened new avenues for biomarker identification. Using targeted metabolomic profiling approach, we have identified that serum branched chain amino acid to histidine ratio is associated with knee OA (Zhai G, et al Ann Rheum Dis 2010). To identify additional novel metabolic biomarkers for OA, we carried out this study using a non-targeted metabolomics approach.
Methods and Subjects:
An available fasting serum sample derived from the TwinsUK cohort was utilized. 1052 Caucasian females were profiled metabolomically using non-targeted approach with LC-MS/MS. Among them, 891 individuals with mean age of 58±10.7 years had knee OA data available. 158 were knee OA cases defined as either having total knee joint replacement due to primary OA (n=22), radiographic knee OA if Kellgren-Lawrence score >=2 (n=72), or self-reported clinical diagnosed knee OA (n=64). 733 were controls with none of these three case definitions. We examined the association between knee OA and the serum metabolomic profile using robust linear regression. Their abundance in each individual's serum sample was measured by the area counts under the MS spectral peak. The area counts were then transformed by natural logarithm to approximate the normal distribution and used in the subsequent analysis after correcting for multiple testing with Bonferroni method.
A total of 275 serum metabolites were identified. We examined the association between each of the 275 serum metabolites and knee OA with adjustment for age, and identified four metabolites associated with knee OA (p <0.00018). g-glutmyl valine was increased in knee OA patients (b=0.42 SD, p=0.00017), which is a confirmation of our previous findings. In addition, we found that a-tocopherol and bilirubin were negatively associated with knee OA (b=-0.47 SD, p=0.00004, and b=-0.43 SD, p=0.0001, respectively), and hyodeoxycholate was positively associated with knee OA (b=0.46 SD, p=0.0001).
This novel study using high-throughput metabolomics confirms our previous findings of valine as a marker of OA and identified an additional three novel serum metabolic biomarkers for knee OA, which could have potential clinical utility.
To cite this abstract, please use the following information:
Zhai, Guangju, Suhre, Karsten, Hart, Deborah, Gieger, Christian, Soranzo, Nicole, Spector, Tim D.; Novel Biomarkers of Knee Osteoarthritis Identified Using a Non-Targeted Metabolomic Approach. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :711