Skip to main content

Advertisement

SpringerLink
Log in

T-Helper 1, T-Helper 2, and T-Regulatory Cytokines Gene Polymorphisms in Irritable Bowel Syndrome

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position −590, IL-4 TT genotype at position −33, and IL-10 GA genotype at position −1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (−330, +160) GT haplotype (P = 0.002), IL-4 (−1098, −590, −33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thompson, W.G., G.F. Longstreth, D.A. Drossman, K.W. Heaton, E.J. Irvine, and S.A. Muller-Lissner. 1999. Functional bowel disorders and functional abdominal pain. Gut 45(Suppl 2):II43–II47.

    Google Scholar 

  2. Jones, R., and S. Lydeard. 1992. Irritable bowel syndrome in the general population. BMJ 304: 87–90.

    Article  CAS  PubMed  Google Scholar 

  3. Lembo, T., J. Munakata, H. Mertz, N. Niazi, A. Kodner, V. Nikas, and E.A. Mayer. 1994. Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome. Gastroenterology 107: 1686–1696.

    CAS  PubMed  Google Scholar 

  4. Mertz, H., B. Naliboff, J. Munakata, N. Niazi, and E.A. Mayer. 1995. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 109: 40–52.

    Article  CAS  PubMed  Google Scholar 

  5. Kellow, J.E., and S.F. Phillips. 1987. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology 92: 1885–1893.

    CAS  PubMed  Google Scholar 

  6. Bazzocchi, G., J. Ellis, J. Villanueva-Meyer, S.N. Reddy, I. Mena, and W.J. Snape Jr. 1991. Effect of eating on colonic motility and transit in patients with functional diarrhea. Simultaneous scintigraphic and manometric evaluations. Gastroenterology 101: 1298–1306.

    CAS  PubMed  Google Scholar 

  7. Chadwick, V.S., W. Chen, D. Shu, B. Paulus, P. Bethwaite, A. Tie, and I. Wilson. 2002. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 122: 1778–1783.

    Article  PubMed  Google Scholar 

  8. Drossman, D.A., D.C. McKee, R.S. Sandler, C.M. Mitchell, E.M. Cramer, B.C. Lowman, and A.L. Burger. 1988. Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology 95: 701–708.

    CAS  PubMed  Google Scholar 

  9. Whitehead, W.E., and O.S. Palsson. 1998. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception. Gastroenterology 115: 1263–1271.

    Article  CAS  PubMed  Google Scholar 

  10. Drossman, D.A., F.H. Creed, G.A. Fava, K.W. Olden, D.L. Patrick, B.B. Toner, and W.E. Whitehead. 1995. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterology International 8: 47–90.

    Google Scholar 

  11. van der Veek, P.P., M. van den Berg, Y.E. de Kroon, H.W. Verspaget, and A.A. Masclee. 2005. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. American Journal of Gastroenterology 100: 2510–2516.

    Article  PubMed  Google Scholar 

  12. Adam, B., T. Liebregts, and G. Holtmann. 2007. Mechanisms of disease: genetics of functional gastrointestinal disorders-searching the genes that matter. Nature Clinical Practice Gastroenterology & Hepatology 4: 102–110.

    Article  CAS  Google Scholar 

  13. Sartor, R.B. 1994. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106: 533–539.

    CAS  PubMed  Google Scholar 

  14. Hoffmann, S.C., E.M. Stanley, E. Darrin Cox, N. Craighead, B.S. DiMercurio, D.E. Koziol, D.M. Harlan, A.D. Kirk, and P.J. Blair. 2001. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 72: 1444–1450.

    Article  CAS  PubMed  Google Scholar 

  15. Melk, A., T. Henne, T. Kollmar, J. Strehlau, K. Latta, G. Offner, G.S. Jhangri, J.H. Ehrich, and C. Von Schnakenburg. 2003. Cytokine single nucleotide polymorphisms and intrarenal gene expression in chronic allograft nephropathy in children. Kidney International 64: 314–320.

    Article  CAS  PubMed  Google Scholar 

  16. Hotoleanu, C., R. Popp, A.P. Trifa, L. Nedelcu, and D.L. Dumitrascu. 2008. Genetic determination of irritable bowel syndrome. World Journal of Gastroenterology 14: 6636–6640.

    Article  CAS  PubMed  Google Scholar 

  17. Amirzargar, A.A., M. Bagheri, A. Ghavamzadeh, K. Alimoghadam, F. Khosravi, N. Rezaei, M. Moheydin, B. Ansaripour, B. Moradi, and B. Nikbin. 2005. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. International Journal of Immunogenetics 32: 167–171.

    Article  CAS  PubMed  Google Scholar 

  18. Amirzargar, A.A., N. Rezaei, H. Jabbari, A.A. Danesh, F. Khosravi, M. Hajabdolbaghi, A. Yalda, and B. Nikbin. 2006. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. European Cytokine Network 17: 84–89.

    CAS  PubMed  Google Scholar 

  19. Mahdaviani, S.A., N. Rezaei, B. Moradi, S. Dorkhosh, A.A. Amirzargar, and M. Movahedi. 2009. Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. Journal of Clinical Immunology 29: 57–62.

    Article  CAS  PubMed  Google Scholar 

  20. Movahedi, M., S.A. Mahdaviani, N. Rezaei, B. Moradi, S. Dorkhosh, and A.A. Amirzargar. 2008. IL-10, TGF-beta, IL-2, IL-12, and IFN-gamma cytokine gene polymorphisms in asthma. Journal of Asthma 45: 790–794.

    Article  CAS  PubMed  Google Scholar 

  21. Rezaei, N., A. Aghamohammadi, Y. Shakiba, M. Mahmoudi, A. Jalali, B. Moradi, and A.A. Amirzargar. 2009. Cytokine gene polymorphisms in common variable immunodeficiency. International Archives of Allergy and Immunology 150: 1–7.

    Article  CAS  PubMed  Google Scholar 

  22. Rezaei, N., A.A. Amirzargar, Y. Shakiba, M. Mahmoudi, B. Moradi, and A. Aghamohammadi. 2009. Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency. Clinical and Experimental Immunology 155: 21–27.

    Article  CAS  PubMed  Google Scholar 

  23. Longstreth, G.F., W.G. Thompson, W.D. Chey, L.A. Houghton, F. Mearin, and R.C. Spiller. 2006. Functional bowel disorders. Gastroenterology 130: 1480–1491.

    Article  PubMed  Google Scholar 

  24. Drossman, D.A., and D.L. Dumitrascu. 2006. Rome III: New standard for functional gastrointestinal disorders. Journal of Gastrointestinal and Liver Diseases 15: 237–241.

    PubMed  Google Scholar 

  25. Amirzargar, A.A., M. Naroueynejad, F. Khosravi, S. Dianat, N. Rezaei, J. Mytilineos, and B. Nikbin. 2008. Cytokine single nucleotide polymorphisms in Iranian populations. European Cytokine Network 19: 104–112.

    CAS  PubMed  Google Scholar 

  26. Vercelli, D. 2002. The regulation of IgE synthesis. Clinical Allergy and Immunology 16: 179–196.

    CAS  PubMed  Google Scholar 

  27. Borish, L.C., and J.W. Steinke. 2003. 2. Cytokines and chemokines. Journal of Allergy and Clinical Immunology 111: S460–475.

    Article  CAS  PubMed  Google Scholar 

  28. Pestka, S., C.D. Krause, D. Sarkar, M.R. Walter, Y. Shi, and P.B. Fisher. 2004. Interleukin-10 and related cytokines and receptors. Annual Review of Immunology 22: 929–979.

    Article  CAS  PubMed  Google Scholar 

  29. Turner, D.M., D.M. Williams, D. Sankaran, M. Lazarus, P.J. Sinnott, and I.V. Hutchinson. 1997. An investigation of polymorphism in the interleukin-10 gene promoter. European Journal of Immunogenetics 24: 1–8.

    CAS  PubMed  Google Scholar 

  30. Gonsalkorale, W.M., C. Perrey, V. Pravica, P.J. Whorwell, and I.V. Hutchinson. 2003. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut 52: 91–93.

    Article  CAS  PubMed  Google Scholar 

  31. Lazarus, R., W.T. Klimecki, L.J. Palmer, D.J. Kwiatkowski, E.K. Silverman, A. Brown, F. Martinez, and S.T. Weiss. 2002. Single-nucleotide polymorphisms in the interleukin-10 gene: differences in frequencies, linkage disequilibrium patterns, and haplotypes in three United States ethnic groups. Genomics 80: 223–228.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research has been supported by Tehran University of Medical Sciences and Health Services grant. The authors are very grateful for all colleagues in the Department of Immunology, School of Medicine, Tehran University of Medical Sciences for their kind help and advice in the laboratory, and all the patients and their families for their kind collaboration in this study.

Author information

Authors and Affiliations

  1. Molecular Immunology Research Center and Immunogenetic Laboratory, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Elham Barkhordari, Mahdi Mahmoudi, Bita Ansaripour, Maryam Alighardashi & Ali Akbar Amirzargar

  2. Growth and Development Research Center, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran

    Nima Rezaei & Pegah Larki

  3. Biochemistry & Nutrition Department, Zanjan Medical University, Zanjan, Iran

    Hamid Reza Ahmadi-Ashtiani

  4. Clinical Biochemistry Department, School of Medical Science, Tarbiat-e-Modarres University, Tehran, Iran

    Hamid Reza Ahmadi-Ashtiani

  5. Gastrointestinal Research Group, University of Calgary, Calgary, AB, Canada

    Mohammad Bashashati

  6. Department of Gastroenterology and Hepatology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Naser Ebrahimi-Daryani

Authors
  1. Elham Barkhordari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nima Rezaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahdi Mahmoudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pegah Larki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hamid Reza Ahmadi-Ashtiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bita Ansaripour
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maryam Alighardashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohammad Bashashati
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ali Akbar Amirzargar
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Naser Ebrahimi-Daryani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naser Ebrahimi-Daryani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barkhordari, E., Rezaei, N., Mahmoudi, M. et al. T-Helper 1, T-Helper 2, and T-Regulatory Cytokines Gene Polymorphisms in Irritable Bowel Syndrome. Inflammation 33, 281–286 (2010). https://doi.org/10.1007/s10753-010-9183-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9183-6

KEY WORDS

Search

Navigation