PMID- 22038405 OWN - NLM STAT- MEDLINE DCOM- 20130125 LR - 20231213 IS - 1529-0131 (Electronic) IS - 0004-3591 (Linking) VI - 63 IP - 11 DP - 2011 Nov TI - Copy number variations of interleukin-17F, interleukin-21, and interleukin-22 are associated with systemic lupus erythematosus. PG - 3487-92 LID - 10.1002/art.30595 [doi] AB - OBJECTIVE: Systemic lupus erythematosus (SLE) represents the classic prototype of systemic autoimmune disease. The identification of the Th17 cell subset has provided new understanding regarding the underlying mechanisms of autoimmunity. Copy number variations (CNVS) have been discovered to have phenotypic consequences and are associated with various types of diseases. We undertook this study to explore a possible association between CNVS of Th17 cell-related genes and the risk of SLE. METHODS: We extracted genomic DNA and RNA from 938 SLE patients and 1,017 healthy controls. We examined CNVS of Th17 cell-related genes, including retinoic acid receptor-related orphan nuclear receptor gammat, STAT-3, interleukin-6 (IL-6), transforming growth factor beta, tumor necrosis factor alpha, IL-17A, IL-17F, IL-21, IL-22, IL-23A, CCL20, and CCR6, and levels of messenger RNA (mRNA) for IL-17F, IL-21, and IL-22. RESULTS: Genotype and allele frequencies for copy number amplifications of IL-17F, IL-21, and IL-22 were found to be significantly higher in SLE patients than in healthy controls. CNVS of IL-17F, IL-21, and IL-22 had no synergistic contribution to SLE. The mRNA expression of IL-17F, IL-21, and IL-22 in the samples with >2 copies of DNA was significantly higher than that in those with 2 copies of DNA. CONCLUSION: Our findings indicate that CNVS of IL-17F, IL-21, and IL-22 are associated with the risk of SLE. CI - Copyright (c) 2011 by the American College of Rheumatology. FAU - Yu, Bo AU - Yu B AD - Shenzhen-PKU-HKUST Medical Center and Shenzhen Hospital, Peking University, Shenzhen, China. FAU - Guan, Ming AU - Guan M FAU - Peng, Yinghui AU - Peng Y FAU - Shao, Yong AU - Shao Y FAU - Zhang, Chao AU - Zhang C FAU - Yue, Xupeng AU - Yue X FAU - Zhang, Jie AU - Zhang J FAU - Yang, Hong AU - Yang H FAU - Zou, Hejian AU - Zou H FAU - Ye, Wencai AU - Ye W FAU - Wan, Jun AU - Wan J FAU - Zhang, Wei AU - Zhang W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arthritis Rheum JT - Arthritis and rheumatism JID - 0370605 RN - 0 (Interleukin-17) RN - 0 (Interleukins) RN - MKM3CA6LT1 (interleukin-21) SB - IM MH - Adolescent MH - Adult MH - Alleles MH - Child MH - DNA Copy Number Variations MH - Female MH - Gene Frequency MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - Interleukin-17/*genetics MH - Interleukins/*genetics MH - Lupus Erythematosus, Systemic/*genetics MH - Male MH - Middle Aged MH - Th17 Cells/*immunology MH - Interleukin-22 EDAT- 2011/11/01 06:00 MHDA- 2013/01/26 06:00 CRDT- 2011/11/01 06:00 PHST- 2011/11/01 06:00 [entrez] PHST- 2011/11/01 06:00 [pubmed] PHST- 2013/01/26 06:00 [medline] AID - 10.1002/art.30595 [doi] PST - ppublish SO - Arthritis Rheum. 2011 Nov;63(11):3487-92. doi: 10.1002/art.30595.