New genes associated with rheumatoid arthritis identified by gene expression profiling
H. Wang
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
These two authors contributed equally to this work.Search for more papers by this authorJ. Guo
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
These two authors contributed equally to this work.Search for more papers by this authorJ. Jiang
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorW. Wu
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorX. Chang
Department of Rheumatology and Immunology, Qianfoshan Hospital, Jinan, China
Search for more papers by this authorH. Zhou
Department of Rheumatology and Immunology, Shenzhen Second People's Hospital, Shenzhen, China
Search for more papers by this authorZ. Li
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
J. Zhao
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Correspondence
Dr. Jinyin Zhao, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Email: [email protected]
Search for more papers by this authorH. Wang
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
These two authors contributed equally to this work.Search for more papers by this authorJ. Guo
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
These two authors contributed equally to this work.Search for more papers by this authorJ. Jiang
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorW. Wu
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Search for more papers by this authorX. Chang
Department of Rheumatology and Immunology, Qianfoshan Hospital, Jinan, China
Search for more papers by this authorH. Zhou
Department of Rheumatology and Immunology, Shenzhen Second People's Hospital, Shenzhen, China
Search for more papers by this authorZ. Li
Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
J. Zhao
The Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
Correspondence
Dr. Jinyin Zhao, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
Email: [email protected]
Search for more papers by this authorSummary
In this study, we aimed to find new genes associated with rheumatoid arthritis (RA) so that more comprehensive genes would be used for monitoring and/or diagnosing patients. Illumina digital gene expression profiling was applied in two sample types – peripheral blood mononuclear cells (PBMCs) and synovial cells to compare the gene expression pattern between 17 patients with RA and three control groups (six osteoarthritis patients, three ankylosing spondylitis patients and 17 healthy controls). Bioinformatics was performed on pathway analysis and protein–protein interaction networks. Four novel genes from PBMCs – DHRS3, TTC38, SAP30BP and LPIN2 – were found to be associated with RA and further confirmed through quantitative real-time polymerase chain reaction. Five new differentially expressed genes (EPYC, LIFR, GLDN, TADA3 and ZNRF3) found in synovial cells were not confirmed. Pathway analyses revealed 10 significantly enriched pathways, and a protein–protein interaction network analysis showed that four novel PBMC-derived genes were connected to previously reported genes by four intermediate genes. Therefore, we proposed that four newly identified PBMC-derived genes could be integrated with previously reported RA-associated genes to monitor and/or diagnose RA.
Supporting Information
Filename | Description |
---|---|
iji12313-sup-0001-SupInfo.docxWord document, 1.9 MB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Arnett, F. C., Edworthy, S. M., Bloch, D. A., Mcshane, D. J., Fries, J. F., Cooper, N. S., … Hunder, G. G. (1988). The American-Rheumatism-Association 1987 Revised Criteria for the Classification of Rheumatoid-Arthritis. Arthritis and Rheumatism, 31, 315–324.
- Ash, M. (2011) Vitamin A: The key to immune tolerance in the gut. Journal of Orthomolecular Medicine, 26, 7–10.
- Barton, A., Thomson, W., Ke, X., Eyre, S., Hinks, A., Bowes, J., … Worthington, J. (2008). Re-evaluation of putative rheumatoid arthritis susceptibility genes in the post-genome wide association study era and hypothesis of a key pathway underlying susceptibility. Human Molecular Genetics, 17, 2274–2279.
- Batliwalla, F. M., Baechler, E. C., Xiao, X., Li, W., Balasubramanian, S., Khalili, H., … Gregersen, P. K. (2005). Peripheral blood gene expression profiling in rheumatoid arthritis. Genes and Immunity, 6, 388–397.
- Benjamini, Y., & Yekutieli, D. (2001). The control of the false discovery rate in multiple testing under dependency. The Annals of Statistics, 29, 1165–1188.
- Bentley, D., Brown, M. A., Cardon, L. R., Caulfield, M., Clayton, D. G., Compston, A., … Worthington, J. (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661–678.
- Dougados, M., Linden, S., & Juhlin, R. (1991). The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis and Rheumatism, 34, 1218–1227.
- Ferguson, P. J., Chen, S., Tayeh, M. K., Ochoa, L., Leal, S. M., Pelet, A., … EI-Shanti, H. (2005). Homozygous mutations in LPIN2 are responsible for the syndrome of chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anaemia (Majeed syndrome). Journal of Medical Genetics, 42, 551–557.
- Firestein, G. S. (2003). Evolving concepts of rheumatoid arthritis. Nature, 423, 356–361.
- Haeseleer, F., Huang, J., Lebioda, L., Saari, J. C., & Palczewski, K. (1998). Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal. The Journal of Biological Chemistry, 273, 21790–21799.
- Hochberg, M. C., Altman, R. D., Brandt, K. D., Clark, B. M., Dieppe, P. A., Griffin, M. R., … Schnitzer, T. J. (1995a). Guidelines for the Medical-Management of Osteoarthritis. 1. Osteoarthritis of the Hip. Arthritis and Rheumatism, 38, 1535–1540.
- Hochberg, M. C., Altman, R. D., Brandt, K. D., Clark, B. M., Dieppe, P. A., Griffin, M. R., … Schnitzer, T. J. (1995b). Guidelines for the Medical-Management of Osteoarthritis. 2. Osteoarthritis of the Knee. Arthritis and Rheumatism, 38, 1541–1546.
- Kirschner, R. D., Rother, K., Muller, G. A., & Engeland, K. (2010). The retinal dehydrogenase/reductase retSDR1/DHRS3 gene is activated by p53 and p63 but not by mutants derived from tumors or EEC/ADULT malformation syndromes. Cell Cycle, 9, 2177–2188.
- Li, J. F., Liu, L. D., Ma, S. H., Che, Y. C., Wang, L. C., Dong, C. H., … Li, Q. H. (2004). HTRP–an immediate-early gene product induced by HSV1 infection in human embryo fibroblasts, is involved in cellular co-repressors. Journal of Biochemistry, 136, 169–176.
- Lydyard, P. M., & Edwards, J. C. (1994). The pathophysiology of rheumatoid arthritis. Clinical and Experimental Rheumatology, 12(Suppl 11), S55–S58.
- Marrack, P., Kappler, J., & Kotzin, B. L. (2001). Autoimmune disease: Why and where it occurs. Nature Medicine, 7, 899–905.
- Medzhitov, R. (2010). Inflammation 2010: New adventures of an old flame. Cell, 140, 771–776.
- Morgan, A. W., Robinson, J. I., Conaghan, P. G., Martin, S. G., Hensor, E. M., Morgan, M. D., … Emery, P. (2010). Evaluation of the rheumatoid arthritis susceptibility loci HLA-DRB1, PTPN22, OLIG3/TNFAIP3, STAT4 and TRAF1/C5 in an inception cohort. Arthritis Research & Therapy, 12, R57–66.
- Nardo, G., Pozzi, S., Pignataro, M., Lauranzano, E., Spano, G., Garbelli, S., … Bonetto, V. (2011). Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells. PLoS One, 6, e25545–25557.
- Padmos, R. C., Schloot, N. C., Beyan, H., Ruwhof, C., Staal, F. J., de Ridder, D., … Drexhage, H. A. (2008). Distinct monocyte gene-expression profiles in autoimmune diabetes. Diabetes, 57, 2768–2773.
- Peterfy, M., Phan, J., Xu, P., & Reue, K. (2001). Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. Nature Genetics, 27, 121–124.
- Pimentel-Santos, F. M., Ligeiro, D., Matos, M., Mourao, A. F., Costa, J., Santos, H., … Thomas, G. P. (2011). Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects. Arthritis Research & Therapy, 13, R57–64.
- Raychaudhuri, S., Remmers, E. F., Lee, A. T., Hackett, R., Guiducci, C., Burtt, N. P., … Plenge, R. M. (2008). Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nature Genetics, 40, 1216–1223.
- Raychaudhuri, S., Sandor, C., Stahl, E. A., Freudenberg, J., Lee, H. S., Jia, X., … Bakker, P. I. (2012). Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nature Genetics, 44, 291–296.
- Richards, T. J., Eggebeen, A., Gibson, K., Yousem, S., Fuhrman, C., Gochuico, B. R., … Ascherman, D. P. (2009). Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis and Rheumatism, 60, 2183–2192.
- Thomson, W., Barton, A., Ke, X., Eyre, S., Hinks, A., Bowes, J., … Worthington, J. (2007). Rheumatoid arthritis association at 6q23. Nature Genetics, 39, 1431–1433.
- Toonen, E. J., Barrera, P., Radstake, T. R., van Riel, P. L., Scheffer, H., Franke, B., & Coenen, M. J. (2008). Gene expression profiling in rheumatoid arthritis: Current concepts and future directions. Annals of the Rheumatic Diseases, 67, 1663–1669.
- Van Halm, V. P., Nielen, M. M. J., Nurmohamed, M. T., van Schaardenburg, D., Reesink, H. W., Voskuyl, A. E., … Dijkmans, B. A. C. (2007). Lipids and inflammation: Serial measurements of the lipid profile of blood donors who later developed rheumatoid arthritis. Annals of the Rheumatic Diseases, 66, 184–188.
- Vanderlinden, S., Valkenburg, H. A., & Cats, A. (1984). Evaluation of Diagnostic-Criteria for Ankylosing-Spondylitis - a Proposal for Modification of the New-York Criteria. Arthritis and Rheumatism, 27, 361–368.
- Zolfaghari, R., Chen, Q., & Ross, A. C. (2012). DHRS3, a retinal reductase, is differentially regulated by retinoic acid and lipopolysaccharide-induced inflammation in THP-1 cells and rat liver. American Journal of Physiology Gastrointestinal and Liver Physiology, 303, G578–588.