Dr. Kim, Mr. Jung, and Dr. J. S. Bae contributed equally to this work.
Systemic Lupus Erythematosus
Deletion Variants of RABGAP1L, 10q21.3, and C4 Are Associated With the Risk of Systemic Lupus Erythematosus in Korean Women
Article first published online: 28 MAR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 4, pages 1055–1063, April 2013
How to Cite
Kim, J.-H., Jung, S.-H., Bae, J. S., Lee, H.-S., Yim, S.-H., Park, S.-Y., Bang, S.-Y., Hu, H.-J., Shin, H. D., Bae, S.-C. and Chung, Y.-J. (2013), Deletion Variants of RABGAP1L, 10q21.3, and C4 Are Associated With the Risk of Systemic Lupus Erythematosus in Korean Women. Arthritis & Rheumatism, 65: 1055–1063. doi: 10.1002/art.37854
- Issue published online: 28 MAR 2013
- Article first published online: 28 MAR 2013
- Accepted manuscript online: 17 JAN 2013 03:37PM EST
- Manuscript Accepted: 27 DEC 2012
- Manuscript Received: 7 MAR 2012
- Korea Healthcare Technology R&D Project. Grant Numbers: A092258, A040002, A111218-11-GM01
- Ministry of Health and Welfare, Republic of Korea
Several copy number variations (CNVs) have been found to be associated with systemic lupus erythematosus (SLE) through the target gene approach. However, genome-wide features of CNVs and their role in the risk of SLE remain unknown. The aim of this study was to identify SLE-associated CNVs in Korean women.
Genome-wide assessments of CNVs were performed in 382 SLE patients and 191 control subjects, using an Illumina HumanHap610 BeadChip genotyping platform. SLE-associated CNV regions that were identified by genome-wide association study (GWAS) were replicated in quantitative polymerase chain reaction (PCR) and deletion-typing PCR analyses in an independent sample set comprising 564 SLE patients and 511 control subjects.
Of 144 common CNV regions, 3 deletion-type CNV regions in 1q25.1, 8q23.3, and 10q21.3 were found to be significantly associated with SLE by GWAS analysis. In the independent replication, the CNV regions in 1q25.1 (RABGAP1L) and 10q21.3 were successfully replicated (odds ratio [OR] 1.30, P = 0.038 and OR 1.90, P = 3.6 × 10−5, respectively), and the associations were confirmed again by deletion-typing PCR. The CNV region in the C4 gene, which showed a potential association in the discovery stage, was included in the replication analysis and was found to be significantly associated with the risk of SLE (OR 1.88, P = 0.01). Through deletion-typing PCR, the exact sizes and breakpoint sequences of the deletions were defined. Individuals with the deletions in all 3 loci (RABGAP1L, 10q21.3, and C4) had a much higher risk of SLE than did those without any deletions in the 3 loci (OR 5.52, P = 3.9 × 10−4).
These CNV regions can be useful to identify the pathogenic mechanisms of SLE, and might be used to more accurately predict the risk of SLE by taking into consideration their synergistic effects on disease susceptibility.