Basic and translational research 4Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23, Uppsala, Sweden. 5Institute of Environmental Medicine, Unit of Immnology and Chronic diseases, Karolinska Institut, 761 77, Solna, Sweden. 6Department of Laboratory Medicine, section of M.I.G., Lund University, 221 00, Lund, Sweden 7Hospital Carlos Haya, 29009, Málaga, Spain 8Hospital Virgen del Rocío, 41013, Sevilla, Spain 9Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain 10Department of Rheumatology, Sanatorio Parque, Rosario, 2000, Argentina 11Department of Medical Sciences and Institute of Research in Chronic Autoimmune Diseases (IRCAD), University of Eastern Piedmont, 28100, Novara, Italy 12Unità Operativa Complessa Reumatología, Azienda Ospedaliera San Camillo- Forlanini, Roma, 00152, Italy 13Hannover Medical School, 30625, Hannover, Germany 14Cliniques Universitaires Saint-Luc, Université catholique de Louvain, 1200 Bruxelles, Belgium 15Department of Pediatrics and Health Center, University of Szeged, H-6721, Szeged, Hungary 16Department of Rheumatology, Albert Szent-Györgyi Clinical Centre, University of Szeged, H-6725, Szeged, Hungary 17Hospital Santo Antonio and Unidade Multidisciplinar em Investigação Biomédica/ IInstituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto, 4099-003, Porto, Portugal 18Unidade Multidisciplinar em Investigação Biomédica/Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto, 4099-003, Porto, Portugal 19Instituto de Parasitología y Biomedicina López Neyra, CSIC, Armilla, Spain. REFERENCES 1. Hom G, Graham RR, Modrek B, et al. Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX. N Engl J Med 2008;358:900–9. 2. Tsuchiya N, Ito I, Kawasaki A. Association of IRF5, STAT4 and BLK with systemic lupus erythematosus and other rheumatic diseases. Nihon Rinsho Meneki Gakkai Kaishi 2010;33:57–65. 3. Ito I, Kawaguchi Y, Kawasaki A, et al. Association of the FAM167A-BLK region with systemic sclerosis. Arthritis Rheum 2010;62:890–5. 4. Torres O, Palomino-Morales R, Vazquez-Rodriguez TR, et al. Role of the C8orf13- BLK region in biopsy-proven giant cell arteritis. Hum Immunol 2010;71:525–9. 5. Yin H, Borghi MO, Delgado-Vega AM, et al. Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome. Arthritis Rheum 2009;60:2468–71. 6. Fan Y, Tao JH, Zhang LP, et al. Association of BLK (rs13277113, rs2248932) polymorphism with systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 2011;38:4445–53. 7. Nordmark G, Kristjansdottir G, Theander E, et al. Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren’s syndrome. Genes Immun 2011;12:100–9. 8. Zhang Z, Zhu KJ, Xu Q, et al. The association of the BLK gene with SLE was replicated in Chinese Han. Arch Dermatol Res 2010;302:619–24. 9. Gourh P, Agarwal SK, Martin E, et al. Association of the C8orf13-BLK region with systemic sclerosis in North-American and European populations. J Autoimmun 2010;34:155–62. 10. Orozco G, Eyre S, Hinks A, et al. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis 2011;70:463–8. 11. Appel S, Filter M, Reis A, et al. Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759. Eur J Hum Genet 2002;10:17–25. 12. Borowiec M, Liew CW, Thompson R, et al. Mutations at the BLK locus linked to maturity onset diabetes of the young and beta-cell dysfunction. Proc Natl Acad Sci USA 2009;106:14460–5. 13. Dymecki SM, Niederhuber JE, Desiderio SV. Speciﬁc expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science 1990;247:332–6. 14. Delgado-Vega A, Sánchez E, Löfgren S, et al. Recent ﬁndings on genetics of systemic autoimmune diseases. Curr Opin Immunol 2010;22:698–705. 15. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classiﬁcation of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–7. 16. Barrett JC. Haploview: Visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009;2009:pdb.ip71. 17. Howie BN, Donnelly P, Marchini J. A ﬂexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet 2009;5:e1000529. 18. Altshuler DM, Gibbs RA, Peltonen L, et al. Integrating common and rare genetic variation in diverse human populations. Nature 2010;467:52–8. 19. International HapMap Consortium. A haplotype map of the human genome. Nature 2005;437:1299–320. 20. 1000 Genomes Consortium. A map of human genome variation from population- scale sequencing. Nature 2010;467:1061–73. 21. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole- genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559–75. 22. Aulchenko YS, Ripke S, Isaacs A, et al. GenABEL: an R library for genome-wide association analysis. Bioinformatics 2007;23:1294–6. 23. Dozmorov MG, Cara LR, Giles CB, et al. GenomeRunner: automating genome exploration. Bioinformatics 2012;28:419–20. 24. Karolchik D, Hinrichs AS, Furey TS, et al. The UCSC Table Browser data retrieval tool. Nucleic Acids Res 2004;32(Database issue):D493–6. 25. Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res 2003;31:3812–14. 26. Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non- synonymous variants on protein function using the SIFT algorithm. Nat Protoc 2009;4:1073–81. 27. Deckert M, Elly C, Altman A, et al. Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases. J Biol Chem 1998;273:8867–74. 28. Rao N, Ghosh AK, Ota S, et al. The non-receptor tyrosine kinase Syk is a target of Cbl-mediated ubiquitylation upon B-cell receptor stimulation. EMBO J 2001;20:7085–95. 29. Welcker M, Singer J, Loeb KR, et al. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell 2003;12:381–92. 30. Hao B, Oehlmann S, Sowa ME, et al. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell 2007;26:131–43. 31. Koepp DM, Schaefer LK, Ye X, et al. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 2001;294:173–7. 32. Strohmaier H, Spruck CH, Kaiser P, et al. Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 2001;413:316–22. 33. Zwollo P, Rao S, Wallin JJ, et al. The transcription factor NF-kappaB/p50 interacts with the blk gene during B cell activation. J Biol Chem 1998;273:18647–55. 1226 Ann Rheum Dis 2012;71:1219–1226. doi:10.1136/annrheumdis-2011-200987