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.


Algorithm Using Genome-Wide SNP Analysis for Prediction of Progression of Joint Destruction in RA Patients from Multiple Medical Cohorts.

Matsubara4,  Tsukasa, Koyano7,  Satoru, Sakai1,  Yoshitada, Funahashi7,  Keiko, Hagiwara5,  Takafumi, Miura4,  Takako, Okuda4,  Kosuke

Himeji Dokkyo University, Himeji, Japan
Inoue Hospital, Takasaki, Japan
Izumihara Rheumatic and Medical Clinic, Kagoshima, Japan
Matsubara Mayflower Hospital, Kato, Japan
Matsubara Mayflower Hospital, Kato, Japan
Matsuno Clinic for Rheumatic Diseases, Toyama, Japan
Research Institute of Joint Diseases, Kobe, Japan
Sagawa Akira Rheumatology Clinic, Sapporo, Japan
Shono Rheumatology Clinic, Fukuoka, Japan

Purpose:

Although not yet fully possible, ideally, the prediction of progression of joint destruction would be pivotal in establishing a strategy of treatment for individual RA patient since patients with rapidly progressing joint destruction need tight initial control. We have developed an SNP algorithm with the aim of enabling the prediction of progression of joint destruction with genome-wide SNP analysis by using multiple medical cohorts.

Patients and Methods:

One-hundred and twenty-seven RA patients whose disease duration was within 5 years were enrolled in this study from 6 hospitals in different regions of Japan. All patients were treated with biologics after the failure of DMARDs therapy. RA joint destruction was estimated by Sharp score. Forty-five patients had a Sharp score of >100 (severe joint destruction), 30 had a score of 100-50 (intermediate joint destruction) and 52 had a score of <50 (mild joint destruction). Genome-wide SNP genotyping was performed by Illumina HumanHap300K chip. Case-control analyses between 278,347 SNPs and joint destruction (severe vs. mild) were examined by Fisher's exact tests. We selected 10 SNPs associated with joint destruction (p < 0.0001). We then scored relationship between each SNP and progress of joint destruction, the estimated total score of 10 SNPs (estimated scoring in each SNP was as follows: homo allele in the majority in severe joint destruction group: +1 point, hetero allele: 0 point, and homo allele in the majority of mild joint destruction group: -1 point), and examined relationships between the severe and mild group, and the total score.

Results:

Accuracy ((true positive+true negative)/total), specificity (true negative/(false positive+true negative)) and sensitivity (true positive/(true positive+false negative)) of the algorithm for distinguishing the severe destruction group from the mild destruction group ranged from 92–97%. It is therefore suggested that the SNP algorithm may enable the prediction of rapidly progressing severe joint destruction.

Conclusion:

This highly accurate algorithm using SNP analysis may be useful in initially distinguishing severe joint destruction, and, in this way, may contribute to establishing a strategy of treatment for individual RA patients.

To cite this abstract, please use the following information:
Matsubara, Tsukasa, Koyano, Satoru, Sakai, Yoshitada, Funahashi, Keiko, Hagiwara, Takafumi, Miura, Takako, et al; Algorithm Using Genome-Wide SNP Analysis for Prediction of Progression of Joint Destruction in RA Patients from Multiple Medical Cohorts. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1738
DOI: 10.1002/art.29503

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