, Volume 37, Issue 3, pp 793–800 | Cite as

JAK2 rs10758669 Polymorphisms and Susceptibility to Ulcerative Colitis and Crohn's Disease: A Meta-analysis

  • Ji-Xiang Zhang
  • Jia Song
  • Jun Wang
  • Wei-Guo Dong


In this meta-analysis, we aimed to clarify the impact of Janus kinase 2 (JAK2) rs10758669 polymorphisms on ulcerative colitis (UC) and Crohn's disease (CD) risk. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 %CIs) were calculated. Eleven studies with 7009 CD patients, 7929 UC patients, and 19235 controls were included. The results showed that JAK2 rs10758669 polymorphism was associated with CD (AC vs. AA, OR = 1.16, 95 %CI, 1.08–1.24; CC vs. AA, OR = 1.29, 95 %CI, 1.17–1.43; AC + CC vs. AA, OR = 1.19, 95 %CI, 1.11–1.27; CC vs. AA + AC, OR = 1.19, 95 %CI, 1.09–1.31; C vs. A, OR = 1.14, 95 %CI, 1.09–1.20) and UC susceptibility (AC vs. AA, OR = 1.14, 95 %CI, 1.06–1.22; CC vs. AA, OR = 1.33, 95 %CI, 1.20–1.47; AC + CC vs. AA, OR = 1.18, 95 %CI, 1.10–1.27; CC vs. AA + AC, OR = 1.24, 95 %CI, 1.12–1.36; C vs. A, OR = 1.15, 95 %CI, 1.10–1.21). But no significant association was found between JAK2 rs10758669 polymorphism with CD in Asian. Either in adult-onset group or multi-age group, hospital-based group or population-based group, JAK2 rs10758669 polymorphism was associated with CD and UC susceptibility. This meta-analysis indicated that JAK2 rs10758669 polymorphism was a risk factor both for CD and UC, especially in Caucasian. The differences in age of onset and study design did not influence the associations obviously. Gene–gene and gene–environment interactions should be investigated in the future.


JAK2 polymorphisms ulcerative colitis Crohn's disease meta-analysis 


  1. 1.
    Leone V, Chang EB, Devkota S. 2011. Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. J Gastroenterol. 2013; 48: 315-321.Google Scholar
  2. 2.
    Hammer HF. Gut microbiota and inflammatory bowel disease. Dig Dis 29: 550-553.Google Scholar
  3. 3.
    Molodecky, N.A., I.S. Soon, D.M. Rabi, W.A. Ghali, M. Ferris, G. Chernoff, E.I. Benchimol, R. Panaccione, S. Ghosh, H.W. Barkema, and G.G. Kaplan. 2012. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142: 46–54.PubMedCrossRefGoogle Scholar
  4. 4.
    Xavier, R.J., and D.K. Podolsky. 2007. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448: 427–434.PubMedCrossRefGoogle Scholar
  5. 5.
    Loftus Jr., E.V. 2004. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 26: 1504–1517.CrossRefGoogle Scholar
  6. 6.
    Neuman, M.G., and R.M. Nanau. 2012. Single-nucleotide polymorphisms in inflammatory bowel disease. Transl Res 160: 45–64.PubMedCrossRefGoogle Scholar
  7. 7.
    Brand, S. 2009. Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut 58: 1152–1167.PubMedCrossRefGoogle Scholar
  8. 8.
    Coskun, M., M. Salem, J. Pedersen, and O.H. Nielsen. 2013. Involvement of JAK/STAT signaling in the pathogenesis of inflammatory bowel disease. Pharmacol Res 76C: 1–8.CrossRefGoogle Scholar
  9. 9.
    Ivanov, I.I., B.S. McKenzie, L. Zhou, C.E. Tadokoro, A. Lepelley, J.J. Lafaille, D.J. Cua, and D.R. Littman. 2006. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121–1133.PubMedCrossRefGoogle Scholar
  10. 10.
    Medrano, L.M., M. García-Magariños, B. Dema, L. Espino, C. Maluenda, I. Polanco, M.Á. Figueredo, M. Fernández-Arquero, and C. Núñez. 2012. Th17-related genes and celiac disease susceptibility. PLoS One 7: e31244.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Mahy, G., J. Mansfield, A.R. Morgan, C. Mowat, W. Newman, O. Palmieri, C.Y. Ponsioen, U. Potocnik, N.J. Prescott, M. Regueiro, J.I. Rotter, R.K. Russell, J.D. Sanderson, M. Sans, J. Satsangi, S. Schreiber, L.A. Simms, J. Sventoraityte, S.R. Targan, K.D. Taylor, M. Tremelling, H.W. Verspaget, M. De Vos, C. Wijmenga, D.C. Wilson, J. Winkelmann, R.J. Xavier, S. Zeissig, B. Zhang, C.K. Zhang, H. Zhao, International IBD Genetics Consortium (IIBDGC), M.S. Silverberg, V. Annese, H. Hakonarson, S.R. Brant, G. Radford-Smith, C.G. Mathew, J.D. Rioux, E.E. Schadt, M.J. Daly, A. Franke, M. Parkes, S. Vermeire, J.C. Barrett, and J.H. Cho. 2012. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119–124.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Jung, C., J.F. Colombel, M. Lemann, L. Beaugerie, M. Allez, J. Cosnes, G. Vernier-Massouille, J.M. Gornet, J.P. Gendre, J.P. Cezard, F.M. Ruemmele, D. Turck, F. Merlin, H. Zouali, C. Libersa, P. Dieudé, N. Soufir, G. Thomas, and J.P. Hugot. 2012. Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms. PLoS One 7: e52223.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Anderson, C.A., D.C. Massey, J.C. Barrett, N.J. Prescott, M. Tremelling, S.A. Fisher, R. Gwilliam, J. Jacob, E.R. Nimmo, H. Drummond, C.W. Lees, C.M. Onnie, C. Hanson, K. Blaszczyk, R. Ravindrarajah, S. Hunt, D. Varma, N. Hammond, G. Lewis, H. Attlesey, N. Watkins, W. Ouwehand, D. Strachan, W. McArdle, C.M. Lewis, Wellcome Trust Case Control Consortium, A. Lobo, J. Sanderson, D.P. Jewell, P. Deloukas, J.C. Mansfield, C.G. Mathew, J. Satsangi, and M. Parkes. 2009. Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology 136: 523–552.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Polgar, N., V. Csongei, M. Szabo, V. Zambo, B.I. Melegh, K. Sumegi, G. Nagy, Z. Tulassay, and B. Melegh. 2012. Investigation of JAK2, STAT3 and CCR6 polymorphisms and their gene-gene interactions in inflammatory bowel disease. Int J Immunogenet 39: 247–252.PubMedCrossRefGoogle Scholar
  15. 15.
    Danoy, P., K. Pryce, J. Hadler, L.A. Bradbury, C. Farrar, J. Pointon, Australo-Anglo-American Spondyloarthritis Consortium, M. Ward, M. Weisman, J.D. Reveille, B.P. Wordsworth, M. Stone, Spondyloarthritis Research Consortium of Canada, W.P. Maksymowych, P. Rahman, D. Gladman, R.D. Inman, and M.A. Brown. 2010. Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease. PLoS Genet 6: e1001195.PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Ferguson, L.R., D.Y. Han, A.G. Fraser, C. Huebner, W.J. Lam, A.R. Morgan, H. Duan, and N. Karunasinghe. 2010. Genetic factors in chronic inflammation: single nucleotide polymorphisms in the STAT-JAK pathway, susceptibility to DNA damage and Crohn's disease in a New Zealand population. Mutat Res 690: 108–115.PubMedCrossRefGoogle Scholar
  17. 17.
    Yang, S.K., Y. Jung, H. Kim, M. Hong, B.D. Ye, and K. Song. 2011. Association of FCGR2A, JAK2 or HNF4A variants with ulcerative colitis in Koreans. Dig Liver Dis 43: 856–861.PubMedCrossRefGoogle Scholar
  18. 18.
    Amre, D.K., D.R. Mack, K. Morgan, D. Israel, C. Deslandres, E.G. Seidman, P. Lambrette, I. Costea, A. Krupoves, H. Fegury, J. Dong, Z. Xhu, G. Grimard, and E. Levy. 2010. Association between genome-wide association studies reported SNPs and pediatric-onset Crohn's disease inCanadian children. Hum Genet 128: 131–135.PubMedCrossRefGoogle Scholar
  19. 19.
    Hirano, A., K. Yamazaki, J. Umeno, K. Ashikawa, M. Aoki, T. Matsumoto, S. Nakamura, T. Ninomiya, T. Matsui, F. Hirai, T. Kawaguchi, M. Takazoe, H. Tanaka, S. Motoya, Y. Kiyohara, T. Kitazono, Y. Nakamura, N. Kamatani, and M. Kubo. 2013. Association study of 71 European Crohn's disease susceptibility loci in a Japanese population. Inflamm Bowel Dis 19: 526–533.PubMedCrossRefGoogle Scholar
  20. 20.
    Asano, K., T. Matsushita, J. Umeno, N. Hosono, A. Takahashi, T. Kawaguchi, T. Matsumoto, T. Matsui, Y. Kakuta, Y. Kinouchi, T. Shimosegawa, M. Hosokawa, Y. Arimura, Y. Shinomura, Y. Kiyohara, T. Tsunoda, N. Kamatani, M. Iida, Y. Nakamura, and M. Kubo. 2009. A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population. Nat Genet 41: 1325–1329.PubMedCrossRefGoogle Scholar
  21. 21.
    Silverberg, M.S., J.H. Cho, J.D. Rioux, D.P. McGovern, J. Wu, V. Annese, J.P. Achkar, P. Goyette, R. Scott, W. Xu, M.M. Barmada, L. Klei, M.J. Daly, C. Abraham, T.M. Bayless, F. Bossa, A.M. Griffiths, A.F. Ippoliti, R.G. Lahaie, A. Latiano, P. Paré, D.D. Proctor, M.D. Regueiro, A.H. Steinhart, S.R. Targan, L.P. Schumm, E.O. Kistner, A.T. Lee, P.K. Gregersen, J.I. Rotter, S.R. Brant, K.D. Taylor, K. Roeder, and R.H. Duerr. 2009. Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nat Genet 41: 216–220.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Prager, M., J. Büttner, V. Haas, D.C. Baumgart, A. Sturm, M. Zeitz, and C. Büning. 2012. The JAK2 variant rs10758669 in Crohn's disease: altering the intestinal barrier as one mechanism of action. Int J Colorectal Dis 27: 565–573.PubMedCrossRefGoogle Scholar
  23. 23.
    Latella, G., and C. Papi. 2012. Crucial steps in the natural history of inflammatory bowel disease. World J Gastroenterol 18: 3790–3799.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Tsianos, E.V., K.H. Katsanos, and V.E. Tsianos. 2012. Role of genetics in the diagnosis and prognosis of Crohn's disease. World J Gastroenterol 18: 105–118.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Stone, C.D. 2012. The economic burden of inflammatory bowel disease: Clear problem, unclear solution. Dig Dis Sci 57: 3042–3044.PubMedCrossRefGoogle Scholar
  26. 26.
    Abraham, C., and J.H. Cho. 2009. Inflammatory bowel disease. N Engl J Med 361: 2066–2078.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Thompson, A.I., and C.W. Lees. 2011. Genetics of ulcerative colitis. Inflamm Bowel Dis 17: 831–848.PubMedCrossRefGoogle Scholar
  28. 28.
    Lee, J.C., and M. Parkes. 2011. Genome-wide association studies and Crohn's disease. Brief Funct Genomics 10(7): 1–76.Google Scholar
  29. 29.
    Murray, P.J. 2007. The JAK-STAT signaling pathway: Input and output integration. J Immunol 178: 2623–2629.PubMedCrossRefGoogle Scholar
  30. 30.
    Parham, C., M. Chirica, J. Timans, E. Vaisberg, M. Travis, J. Cheung, S. Pflanz, R. Zhang, K.P. Singh, F. Vega, W. To, J. Wagner, A.M. O'Farrell, T. McClanahan, S. Zurawski, C. Hannum, D. Gorman, D.M. Rennick, R.A. Kastelein, Malefyt R. de Waal, and K.W. Moore. 2002. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168: 5699–5708.PubMedCrossRefGoogle Scholar
  31. 31.
    Szabo, S.J., S.T. Kim, G.L. Costa, X. Zhang, C.G. Fathman, and L.H. Glimcher. 2000. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655–669.PubMedCrossRefGoogle Scholar
  32. 32.
    Stritesky, G.L., R. Muthukrishnan, S. Sehra, R. Goswami, D. Pham, J. Travers, E.T. Nguyen, D.E. Levy, and M.H. Kaplan. 2011. The transcription factor STAT3 is required for T helper 2 cell development. Immunity 34: 39–49.PubMedCentralPubMedCrossRefGoogle Scholar
  33. 33.
    Durant, L., W.T. Watford, H.L. Ramos, A. Laurence, G. Vahedi, L. Wei, H. Takahashi, H.W. Sun, Y. Kanno, F. Powrie, and J.J. O'Shea. 2010. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32: 605–615.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Strober, W. 2008. Why study animal models of IBD? Inflamm Bowel Dis 14(Suppl 2): S129–S131.PubMedCrossRefGoogle Scholar
  35. 35.
    Imielinski, M., R.N. Baldassano, A. Griffiths, R.K. Russell, V. Annese, M. Dubinsky, S. Kugathasan, J.P. Bradfield, T.D. Walters, P. Sleiman, C.E. Kim, A. Muise, K. Wang, J.T. Glessner, S. Saeed, H. Zhang, E.C. Frackelton, C. Hou, J.H. Flory, G. Otieno, R.M. Chiavacci, R. Grundmeier, M. Castro, A. Latiano, B. Dallapiccola, J. Stempak, D.J. Abrams, K. Taylor, D. McGovern, Western Regional Alliance for Pediatric IBD, G. Silber, I. Wrobel, A. Quiros, International IBD Genetics Consortium, C. Libioulle, C. Sandor, M. Lathrop, J. Belaiche, O. Dewit, I. Gut, S. Heath, D. Laukens, M. Mni, P. Rutgeerts, A. Van Gossum, D. Zelenika, D. Franchimont, J.P. Hugot, M. de Vos, S. Vermeire, E. Louis, Belgian-French IBD Consortium; Wellcome Trust Case Control Consortium, L.R. Cardon, C.A. Anderson, H. Drummond, E. Nimmo, T. Ahmad, N.J. Prescott, C.M. Onnie, S.A. Fisher, J. Marchini, J. Ghori, S. Bumpstead, R. Gwillam, M. Tremelling, P. Delukas, J. Mansfield, D. Jewell, J. Satsangi, C.G. Mathew, M. Parkes, M. Georges, M.J. Daly, M.B. Heyman, G.D. Ferry, B. Kirschner, J. Lee, J. Essers, R. Grand, M. Stephens, A. Levine, D. Piccoli, J. Van Limbergen, S. Cucchiara, D.S. Monos, S.L. Guthery, L. Denson, D.C. Wilson, S.F. Grant, M. Daly, M.S. Silverberg, J. Satsangi, and H. Hakonarson. 2009. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet 41: 1335.PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Essers, J.B., J.J. Lee, S. Kugathasan, C.R. Stevens, R.J. Grand, M.J. Daly, and NIDDK IBD Genetics Consortium. 2009. Established genetic risk factors do not distinguish early and later onset Crohn's disease. Inflamm Bowel Dis 15: 1508–1514.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Ji-Xiang Zhang
    • 1
  • Jia Song
    • 1
  • Jun Wang
    • 1
  • Wei-Guo Dong
    • 1
  1. 1.Department of GastroenterologyRenmin Hospital of Wuhan UniversityWuhanChina

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