Digestive Diseases and Sciences

, Volume 52, Issue 7, pp 1632–1635 | Cite as

Crohn’s Disease and SLC11A1 Promoter Polymorphism

  • Irit Chermesh
  • Aviva Azriel
  • Michal Alter-Koltunoff
  • Rami Eliakim
  • Amir Karban
  • Ben Zion Levi


Crohn’s disease (CD) is a chronic multifactorial inflammatory disease. The prevalence of CD in Ashkenazi Jews is higher than in Sephardic Jews. SLC11A1, also known as Nramp1, is a divalent cation antiporter essential for the elimination of intraphagosomal pathogens. SLC11A1 has seven alleles in the promoter region and previous studies have suggested an association between CD and SLC11A1. The aim of this study was to check for a possible association between SLC11A1 promoter alleles and CD in Ashkenazi Jewish patients. DNA samples from healthy Ashkenazi donors and Ashkenazi CD patients were obtained and analyzed for SLC11A1 promoter polymorphism by PCR and DNA sequencing. One hundred thirty-one samples from healthy donors and 131 samples from CD patients were analyzed. Four alleles were identified: ∼70% of the samples carried allele 3; ∼30%, allele 2; ∼1%, allele 1; and <1%, allele 5. There was no difference in allele frequencies between healthy donors and CD patients. No correlation was found between mutations in NOD2/CARD15 and the phenotype of CD. We conclude that the difference in SLC11A1 promoter polymorphism plays no role in CD in Ashkenazi Jews.


Crohn’s disease SLC11A1 NRAMP Promoter polymorphism Alleles Genetics Ulcerative colitis Inflammatory bowel disease 



We are grateful to Drs. Darvasi and Yakir of the Hebrew University in Jerusalem for their help with statistical analysis. This research was supported by the Broad Medical Research Program of The Eli and Edythe L. Broad Foundation to B.Z.L. and R.E.


  1. 1.
    Ogura Y, Bonen DK, Inohara N, et al. (2001) A frameshift mutation in NOD2/CARD15 associated with susceptibility to Crohn’s disease. Nature 411(6837):603–606PubMedCrossRefGoogle Scholar
  2. 2.
    Karban A, Waterman M, Panhuysen CI, et al. (2004) NOD2/CARD15 genotype and phenotype differences between Ashkenazi and Sephardic Jews with Crohn’s disease. Am J Gastroenterol 99(6):1134–1140PubMedCrossRefGoogle Scholar
  3. 3.
    Fidder HH, Olschwang S, Avidan B, et al. (2003) Association between mutations in the CARD15 (NOD2) gene and Crohn’s disease in Israeli Jewish patients. Am J Med Genet A 121(3):240–244PubMedCrossRefGoogle Scholar
  4. 4.
    Graham AM, Dollinger MM, Howie SE, et al. (2000) Identification of novel alleles at a polymorphic microsatellite repeat region in the human NRAMP1 gene promoter: analysis of allele frequencies in primary biliary cirrhosis. J Med Genet 37:150–152PubMedCrossRefGoogle Scholar
  5. 5.
    Searle S, Blackwell JM (1999) Evidence for a functional repeat polymorphism in the promoter of the human NRAMP1 gene that correlates with autoimmune versus infectious disease susceptibility. J Med Genet 36:295–299PubMedGoogle Scholar
  6. 6.
    John S, Myerscough A, Marlow A, et al. (1998) Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic heterogeneity. Ann Rheum Dis 57(6):361–365PubMedCrossRefGoogle Scholar
  7. 7.
    Sanjeevi CB, Miller EN, Dabadghao P, et al. (2000) Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis. Arth Rheum 43(6):1397–1404CrossRefGoogle Scholar
  8. 8.
    Abel L, Sanchez FO, Oberti J, et al. (1998) Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 177(1):133–145PubMedCrossRefGoogle Scholar
  9. 9.
    Bellamy R (1999) The natural resistance-associated macrophage protein and susceptibility to intracellular pathogens. Microbes Infect 1(1):23–27PubMedCrossRefGoogle Scholar
  10. 10.
    Sechi LA, Gazouli M, Ikonomopoulos J, et al. (2005) Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn’s disease, and Sardinians: the way ahead. J Clin Microbiol 43(10):5275–5277PubMedCrossRefGoogle Scholar
  11. 11.
    Sechi LA, Scanu AM, Molicotti P, et al. (2005) Detection and Isolation of Mycobacterium avium subspecies paratuberculosis from intestinal mucosal biopsies of patients with and without Crohn’s disease in Sardinia. Am J Gastroenterol 100(7):1529–1536PubMedCrossRefGoogle Scholar
  12. 12.
    Hofmeister A, Neibergs HL, Pokorny RM, et al. (1997) The natural resistance-associated macrophage protein gene is associated with Crohn’s disease. Surgery 122(2):173–178, discussion 178–179PubMedCrossRefGoogle Scholar
  13. 13.
    Kojima Y, Kinouchi Y, Takahashi S, et al. (2001) Inflammatory bowel disease is associated with a novel promoter polymorphism of natural resistance-associated macrophage protein 1 (NRAMP1) gene. Tissue Antigens 58(6):379–384PubMedCrossRefGoogle Scholar
  14. 14.
    Blackwell JM, Searle S, Mohamed H, et al. (2003) Divalent cation transport and susceptibility to infectious and autoimmune disease: continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story. Immunol Lett 85:197–203PubMedCrossRefGoogle Scholar
  15. 15.
    Crawford NP, Eichenberger MR, Colliver DW, et al. (2005) Evaluation of SLC11A1 as an inflammatory bowel disease candidate gene. BMC Med Genet 9:6–10Google Scholar
  16. 16.
    Podolsky DK (1991) Inflammatory bowel disease (2). N Engl J Med 325(14):1008–1016 (review)PubMedCrossRefGoogle Scholar
  17. 17.
    Gasche C, Scholmerich J, Brynskov J, et al. (2000) A simple classification of Crohn’s disease: report of the Working Party for the World Congresses of Gastroenterology, Vienna 1998. Inflamm Bowel Dis 6(1):8–15PubMedCrossRefGoogle Scholar
  18. 18.
    Manichanh C, Rigottier-Gois L, Bonnaud E, Gloux K, Pelletier E, Frangeul L, Nalin R, Jarrin C, Chardon P, Marteau P, Roca J, Dore J. (2006) Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 55(2):205–211Google Scholar
  19. 19.
    Madsen KL (2001) Inflammatory bowel disease: lessons from the IL-10 gene-deficient mouse. Clin Invest Med 24(5):250–257PubMedGoogle Scholar
  20. 20.
    Wild GE (2004) The role of antibiotics in the management of Crohn’s disease. Inflamm Bowel Dis 10(3):321–323PubMedCrossRefGoogle Scholar
  21. 21.
    Fedorak RN, Madsen KL (2004) Probiotics and prebiotics in gastrointestinal disorders. Curr Opin Gastroenterol 20(2):146–155PubMedCrossRefGoogle Scholar
  22. 22.
    Hugot JP, Chamaillard M, Zouali H, et al. (2001) Association of NOD2/CARD15 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Irit Chermesh
    • 1
  • Aviva Azriel
    • 2
  • Michal Alter-Koltunoff
    • 2
  • Rami Eliakim
    • 1
  • Amir Karban
    • 1
  • Ben Zion Levi
    • 2
  1. 1.Department of GastroenterologyRambam Medical CenterHaifaIsrael
  2. 2.Department of Biotechnology and Food EngineeringTechnionHaifaIsrael

Personalised recommendations