Drs. Zhou and Jong Eun Lee contributed equally to this work.
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Systemic Sclerosis
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HLA–DPB1 and DPB2 are genetic loci for systemic sclerosis: A genome-wide association study in Koreans with replication in North Americans
Article first published online: 30 NOV 2009
DOI: 10.1002/art.24982
Copyright © 2009 by the American College of Rheumatology
Additional Information
How to Cite
Zhou, X., Lee, J. E., Arnett, F. C., Xiong, M., Park, M. Y., Yoo, Y. K., Shin, E. S., Reveille, J. D., Mayes, M. D., Kim, J. H., Song, R., Choi, J. Y., Park, J. A., Lee, Y. J., Lee, E. Y., Song, Y. W. and Lee, E. B. (2009), HLA–DPB1 and DPB2 are genetic loci for systemic sclerosis: A genome-wide association study in Koreans with replication in North Americans. Arthritis & Rheumatism, 60: 3807–3814. doi: 10.1002/art.24982
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Drs. Zhou and Jong Eun Lee contributed equally to this work.
Publication History
- Issue published online: 30 NOV 2009
- Article first published online: 30 NOV 2009
- Manuscript Accepted: 18 AUG 2009
- Manuscript Received: 4 MAR 2009
Funded by
- Korean Health 21 Research & Development Project
- Ministry of Health, Welfare, and Family Affairs, Republic of Korea. Grant Number: A030001
- NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases). Grant Numbers: P50-AR-054144, NO1-AR-02251, UL1-RR-024148
- US Department of the Army, Medical Research Acquisition Activity. Grant Numbers: PR-064803, PR-064851
Abstract
Objective
To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.
Methods
A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.
Results
The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA–DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P = 8.16 × 10−13). Subtyping analysis of HLA–DPB1 showed that DPB1*1301 (P = 7.61 × 10−8) and DPB1*0901 (P = 2.55 × 10−5) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti–DNA topoisomerase I (P = 7.58 × 10−17/4.84 × 10−16) or anticentromere autoantibodies (P = 1.12 × 10−3/3.2 × 10−5), respectively.
Conclusion
The results of our genome-wide association study in Korean subjects indicate that the region of HLA–DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA–DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti–DNA topoisomerase I or anticentromere autoantibodies.