[1] Yarwood, A., Huizinga, T. W. J., & Worthington, J. (2016). The genetics of rheumatoid arthritis: Risk and protection in different stages of the evolution of RA. Rheumatology (Oxford, England), 55(2), 199–209. https://doi.org/10.1093/rheumatology/keu323

[2] Lin, Y.-J., Anzaghe, M., & Schülke, S. (2020). Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells, 9(4), 880. Advance online publication. https://doi.org/10.3390/cells9040880

[3] Eijkelenboom, A., & Burgering, B. M. T. (2013). FOXOs: Signalling integrators for homeostasis maintenance. Nature Reviews. Molecular Cell Biology, 14, 83–97. https://doi.org/10.1038/nrm3507

[4] Wang, M., Zhang, X., Zhao, H., Wang, Q., & Pan, Y. (2009). FoxO gene family evolution in vertebrates. BMC Evolutionary Biology, 9, 222. https://doi.org/10.1186/1471-2148-9-222

[5] Kuo, C.-C., & Lin, S.-C. (2007). Altered FOXO1 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Molecular Medicine (Cambridge, Mass.), 13, 561–566. https://doi.org/10.2119/2007- 00021.Kuo

[6] Hosaka, T., Biggs, W. H., III, Tieu, D., Boyer, A. D., Varki, N. M., Cavenee, W. K., & Arden, K. C. (2004). Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proceedings of the National Academy of Sciences of the United States of America, 101(9), 2975–2980. https://doi.org/10.1073/pnas.0400093101

[7] Furuyama, T., Kitayama, K., Shimoda, Y., Ogawa, M., Sone, K., Yoshida-Araki, K., Hisatsune, H., Nishikawa, S., Nakayama, K., Nakayama, K., Ikeda, K., Motoyama, N., & Mori, N. (2004). Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice. The Journal of Biological Chemistry, 279(33), 34741– 34749. https://doi.org/10.1074/jbc.M314214200

[8] Accili, D., & Arden, K. C. (2004). FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 117(4), 421–426. https://doi.org/10.1016/S0092-8674(04)00452-0

[9] Luo, C. T., & Li, M. O. (2018). Foxo transcription factors in T cell biology and tumor immunity. Seminars in Cancer Biology, 50, 13–20. Elsevier. https://doi.org/10.1016/j.semcancer.2018.04.006

[10] Su, D., Coudriet, G. M., Hyun Kim, D., Lu, Y., Perdomo, G., Qu, S., Slusher, S., Tse, H. M., Piganelli, J., Giannoukakis, N., Zhang, J., & Dong, H. H. (2009). FoxO1 links insulin resistance to proinflammatory cytokine IL-1β production in macrophages. Diabetes, 58(11), 2624–2633. https://doi.org/10.2337/db09-0232

[11] Nwadozi, E., Roudier, E., Rullman, E., Tharmalingam, S., Liu, H. Y., Gustafsson, T., & Haas, T. L. (2016). Endothelial FoxO proteins impair insulin sensitivity and restrain muscle angiogenesis in response to a high-fat diet. The FASEB Journal, 30(9), 3039–3052. https://doi.org/10.1096/fj.201600245R

[12] Zhu, M., Goetsch, S. C., Wang, Z., Luo, R., Hill, J. A., Schneider, J., Morris, S. M., Jr., & Liu, Z.-P. (2015). FoxO4 promotes early inflammatory response upon myocardial infarction via endothelial Arg1. Circulation Research, 117(11), 967–977. https://doi.org/10.1161/CIRCRESAHA.115.306919

[13] Viatte, S., Plant, D., & Raychaudhuri, S. (2013). Genetics and epigenetics of rheumatoid arthritis. Nature Reviews. Rheumatology, 9, 141–153. https://doi.org/10.1038/nrrheum.2012.237

[14] Issa, J.-P. J., Ottaviano, Y. L., Celano, P., Hamilton, S. R., Davidson, N. E., & Baylin, S. B. (1994). Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nature Genetics, 7, 536–540. https://doi.org/10.1038/ng0894-536

[15] Esteller, M. (2002). CpG island hypermethylation and tumor suppressor genes: A booming present, a brighter future. Oncogene, 21, 5427–5440. https://doi.org/10.1038/sj.onc.1205600

[16] Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes & Development, 16, 6– 21. https://doi.org/10.1101/gad.947102

[17] Vihinen, M., & Mäntsälä, P. (1989). Microbial amylolytic enzymes. Critical Reviews in Biochemistry and Molecular Biology, 24(4), 329–418. https://doi.org/10.3109/10409238909082556

[18] Aslani, S., Mahmoudi, M., Karami, J., Jamshidi, A. R., Malekshahi, Z., & Nicknam, M. H. (2016). Epigenetic alterations underlying autoimmune diseases. Autoimmunity, 49(2), 69–83. https://doi.org/10.3109/08916934.2015.1134511

[19] Liu, C.-C., Fang, T.-J., Ou, T.-T., Wu, C.-C., Li, R.-N., Lin, Y.-C., Lin, C.-H., Tsai, W.-C., Liu, H.- W., & Yen, J.-H. (2011). Global DNA methylation, DNMT1, and MBD2 in patients with rheumatoid arthritis. Immunology Letters, 135(1–2), 96–99. https://doi.org/10.1016/j.imlet.2010.10.003

[20] Miao, C. G., Yang, Y. Y., He, X., & Li, J. (2013). New advances of DNA methylation and histone modifications in rheumatoid arthritis, with special emphasis on MeCP2. Cellular Signalling, 25(4), 875– 882. https://doi.org/10.1016/j.cellsig.2012.12.017

[21] Glossop, J. R., Emes, R. D., Nixon, N. B., Packham, J. C., Fryer, A. A., Mattey, D. L., & Farrell, W. E. (2016). Genome-wide profiling in treatment-naive early rheumatoid arthritis reveals DNA methylome changes in T and B lymphocytes. Epigenomics, 8(2), 209–224. https://doi.org/10.2217/epi.15.103

[22] de Andres, M. C., Perez-Pampin, E., Calaza, M., Santaclara, F. J., Ortea, I., Gomez-Reino, J. J., & Gonzalez, A. (2015). Assessment of global DNA methylation in peripheral blood cell subpopulations of early rheumatoid arthritis before and after methotrexate. Arthritis Research & Therapy, 17, 233. https://doi.org/10.1186/s13075-015-0748-5

[23] Brown, P. M., Pratt, A. G., & Isaacs, J. D. (2016). Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers. Nature Reviews. Rheumatology, 12, 731–742. https://doi.org/10.1038/nrrheum.2016.175

[24] Wang, Y.-C., & Chiang, E.-P. I. (2012). Lowdose methotrexate inhibits methionine Sadenosyltransferase in vitro and in vivo. Molecular Medicine (Cambridge, Mass.), 18, 423–432. https://doi.org/10.2119/molmed.2011.00048

[25] Nesher, G., & Moore, T. L. (1990). The in vitro effects of methotrexate on peripheral blood mononuclear cells. Modulation by methyl donors and spermidine. Arthritis and Rheumatism, 33(7), 954–959. https://doi.org/10.1002/art.1780330706

[26] Kim, Y. I., Logan, J. W., Mason, J. B., & Roubenoff, R. (1996). DNA hypomethylation in inflammatory arthritis: Reversal with methotrexate. The Journal of Laboratory and Clinical Medicine, 128(2), 165–172. https://doi.org/10.1016/S0022-2143(96)90008-6

[27] Pfaffl, M. W. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research, 29(9), e45. https://doi.org/10.1093/nar/29.9.e45

[28] Miller, S. A., Dykes, D. D., & Polesky, H. F. (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Research, 16(3), 1215. https://doi.org/10.1093/nar/16.3.1215

[29] Li, L.-C., & Dahiya, R. (2002). MethPrimer: Designing primers for methylation PCRs. Bioinformatics (Oxford, England), 18(11), 1427–1431. https://doi.org/10.1093/bioinformatics/18.11.1427

[30] Carlsson, P., & Mahlapuu, M. (2002). Forkhead transcription factors: Key players in development and metabolism. Developmental Biology, 250(1), 1– 23. https://doi.org/10.1006/dbio.2002.0780

[31] Kaestner, K. H., Knöchel, W., & Martínez, D. E. (2000). Unified nomenclature for the winged helix/forkhead transcription factors. Genes & Development, 14, 142– 146. https://doi.org/10.1101/gad.14.2.142

[32] Burgering, B. M. T., & Kops, G. J. P. L. (2002). Cell cycle and death control: Long live Forkheads. Trends in Biochemical Sciences, 27(7), 352–360. https://doi.org/10.1016/S0968-0004(02)02113-8

[33] Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003). Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology, 4, 330–336. https://doi.org/10.1038/ni904

[34] Grabiec, A. M., Angiolilli, C., Hartkamp, L. M., van Baarsen, L. G. M., Tak, P. P., & Reedquist, K. A. (2015). JNK-dependent downregulation of FoxO1 is required to promote the survival of fibroblast-like synoviocytes in rheumatoid arthritis. Annals of the Rheumatic Diseases, 74(9), 1763–1771. https://doi.org/10.1136/annrheumdis-2013-203610

[35] Lin, Y., & Luo, Z. (2017). Aberrant methylation patterns affect the molecular pathogenesis of rheumatoid arthritis. International Immunopharmacology, 46, 141–145. https://doi.org/10.1016/j.intimp.2017.02.008

[36] Karouzakis, E., Gay, R. E., Michel, B. A., Gay, S., & Neidhart, M. (2009). DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthritis and Rheumatism, 60(12), 3613–3622. https://doi.org/10.1002/art.25018

[37] Nakano, K., Whitaker, J. W., Boyle, D. L., Wang, W., & Firestein, G. S. (2013). DNA methylome signature in rheumatoid arthritis. Annals of the Rheumatic Diseases, 72(1), 110–117. https://doi.org/10.1136/annrheumdis-2012-201526

[38] Karami, J., Aslani, S., Tahmasebi, M. N., Mousavi, M. J., Sharafat Vaziri, A., Jamshidi, A., Farhadi, E., & Mahmoudi, M. (2020). Epigenetics in rheumatoid arthritis; Fibroblast-like synoviocytes as an emerging paradigm in the pathogenesis of the disease. Immunology and Cell Biology, 98(3), 171– 186. https://doi.org/10.1111/imcb.12311

[39] Gosselt, H. R., van Zelst, B. D., de Rotte, M. C. F. J., Hazes, J. M. W., de Jonge, R., & Heil, S. G. (2019). Higher baseline global leukocyte DNA methylation is associated with MTX non-response in early RA patients. Arthritis Research & Therapy, 21, 157. https://doi.org/10.1186/s13075-019-1936-5