Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.
This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.
Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position −174 (P = 0.002), and TNF-α G allele at position −238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (−174) and TNF-α GG genotype (−238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (−174) and TNF-α GA genotype (−238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (−174, nt565) GG haplotype and TNF-α (−308, −238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P < 0.001).
IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.
- Thompson WG, Longstreth GF, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(Suppl 2):II43–7. CrossRef
- Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ. 1992;304(6819):87–90. CrossRef
- Kellow JE, Phillips SF. Altered small bowel motility in irritable bowel syndrome is correlated with symptoms. Gastroenterology. 1987;92(6):1885–93.
- Bazzocchi G, Ellis J, Villanueva-Meyer J, et al. Effect of eating on colonic motility and transit in patients with functional diarrhea. Simultaneous scintigraphic and manometric evaluations. Gastroenterology. 1991;101(5):1298–306.
- Lembo T, Munakata J, Mertz H, et al. Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome. Gastroenterology. 1994;107(6):1686–96.
- Mertz H, Naliboff B, Munakata J, et al. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology. 1995;109(1):40–52. CrossRef
- King TS, Elia M, Hunter JO. Abnormal colonic fermentation in irritable bowel syndrome. Lancet. 1998;352(9135):1187–9. CrossRef
- Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122(7):1778–83. CrossRef
- Drossman DA, McKee DC, Sandler RS, et al. Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology. 1988;95(3):701–8.
- Whitehead WE, Palsson OS. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception. Gastroenterology. 1998;115(5):1263–71. CrossRef
- Drossman DA, Creed FH, Fava GA, et al. Psychosocial aspects of the functional gastrointestinal disorders. Gastroenterol Int. 1995;8:47–90.
- Bengtson MB, Ronning T, Vatn MH, et al. Irritable bowel syndrome in twins: genes and environment. Gut. 2006;55(12):1754–9. CrossRef
- Kalantar JS, Locke GR 3rd, Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome: a prospective study. Gut. 2003;52(12):1703–7. CrossRef
- Saito YA, Petersen GM, Locke GR 3rd, et al. The genetics of irritable bowel syndrome. Clin Gastroenterol Hepatol. 2005;3(11):1057–65. CrossRef
- Saito YA, Talley NJ. Genetics of irritable bowel syndrome. Am J Gastroenterol. 2008;103(8):2100–4. quiz 5. CrossRef
- van der Veek PP, van den Berg M, de Kroon YE, et al. Role of tumor necrosis factor-alpha and interleukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol. 2005;100(11):2510–6. CrossRef
- Adam B, Liebregts T, Holtmann G. Mechanisms of disease: genetics of functional gastrointestinal disorders—searching the genes that matter. Nat Clin Pract Gastroenterol Hepatol. 2007;4(2):102–10. CrossRef
- Talley NJ. Genes and environment in irritable bowel syndrome: one step forward. Gut. 2006;55(12):1694–6. CrossRef
- Hotoleanu C, Popp R, Trifa AP, et al. Genetic determination of irritable bowel syndrome. World J Gastroenterol. 2008;14(43):6636–40. CrossRef
- Sartor RB. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology. 1994;106(2):533–9.
- Hoffmann SC, Stanley EM, Darrin Cox E, et al. Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation. 2001;72(8):1444–50. CrossRef
- Melk A, Henne T, Kollmar T, et al. Cytokine single nucleotide polymorphisms and intrarenal gene expression in chronic allograft nephropathy in children. Kidney Int. 2003;64(1):314–20. CrossRef
- Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–91. CrossRef
- Drossman DA, Dumitrascu DL. Rome III: new standard for functional gastrointestinal disorders. J Gastrointestin Liver Dis. 2006;15(3):237–41.
- Amirzargar AA, Naroueynejad M, Khosravi F, et al. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw. 2008;19(2):104–12.
- Amirzargar AA, Rezaei N, Jabbari H, et al. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. Eur Cytokine Netw. 2006;17(2):84–9.
- Mahdaviani SA, Rezaei N, Moradi B, et al. Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. J Clin Immunol. 2009;29(1):57–62. CrossRef
- Rezaei N, Amirzargar AA, Shakiba Y, et al. Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency. Clin Exp Immunol. 2009;155(1):21–7. CrossRef
- Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007;132(3):913–20. CrossRef
- Tilg H, Trehu E, Atkins MB, et al. Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood. 1994;83(1):113–8.
- Fishman D, Faulds G, Jeffery R, et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest. 1998;102(7):1369–76. CrossRef
- Borish LC, Steinke JW. Cytokines and chemokines. J Allergy Clin Immunol. 2003;111(2 Suppl):S460–75. CrossRef
- Rugtveit J, Brandtzaeg P, Halstensen TS, et al. Increased macrophage subset in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut. 1994;35(5):669–74. CrossRef
- Bode H, Schmitz H, Fromm M, et al. IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon. Cytokine. 1998;10(6):457–65. CrossRef
- Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006;130(2):304–11. CrossRef
- Amirzargar AA, Bagheri M, Ghavamzadeh A, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet. 2005;32(3):167–71. CrossRef
- Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome
Journal of Clinical Immunology
Volume 30, Issue 1 , pp 74-79
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Genetic polymorphism
- irritable bowel syndrome IL-6
- Industry Sectors
- Author Affiliations
- 1. Department of Gastroenterology and Hepatology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
- 2. Growth and Development Research Center, Pediatrics Center of Excellence, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- 3. Molecular Immunology Research Center; and Immunogenetic Laboratory, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- 4. Biochemistry & Nutrition Department, Zanjan Medical University, Zanjan, Iran and Clinical Biochemistry Department, Tarbiat-e-Modarres University, Tehran, Iran
- 5. Department of Surgery, Iran University of Medical Sciences, Tehran, Iran
- 6. Gastrointestinal Research Group, University of Calgary, Calgary, AB, Canada