Clinical parameters of inflammatory bowel disease in children do not correlate with four common polymorphisms of the transforming growth factor β1 gene
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Transforming growth factor β1 (TGF-β1) is a cytokine affecting cell proliferation and development, which also has an immunomodulatory activity. Correlations between polymorphisms of the TGF-β1 gene and clinical parameters of inflammatory bowel disease (IBD) were reported previously in adults. Here, we tested whether such correlations occur in pediatric patients suffering from IBD. One hundred and four pediatric IBD patients were involved in this study. Among them, 36 were diagnosed with Crohn's Disease (CD) and 68 were diagnosed with ulcerative colitis (UC). The control group consisted of 103 children, in which IBD was excluded. TGF-β1 levels were determined in plasma and intestinal mucosa samples. The presence of the TGF β1 protein and the amount of TGF β1 mRNA were estimated in intestinal mucosa by immunohistochemistry and reverse transcription Real-Time PCR, respectively. Four common polymorphisms of the TGF-β1 gene were investigated: -800G/A, -509C/T, 869T/C and 915G/C. No significant correlation between TGF-β1 genotypes and (i) TGF-β1 levels in plasma and tissue samples, (ii) TGF-β1 gene expression efficiency in intestinal mucosa, (iii) IBD clinical parameters and (iv) inflammatory activity could be detected in children suffering from IBD. We conclude that, contrary to previous suggestions, the four common polymorphisms of the TGF-β1 gene do not influence the susceptibility to or clinical parameters of IBD in the tested population of children.
- Bayat A, Watson JS, Stanley JK, Ferguson MW, Ollier WE (2002) Novel single nucleotide polymorphisms in the 3'-UTR of the TGFbetaRI and TGFbetaRIII genes. Eur J Immunogenet 29: 445-446.
- Cambien F, Ricard S, Troesch A, Mallet C, Générénaz L, Evans A, Arveiler D, Luc G, Ruidavets JB, Poirier O (1996) Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Témoin de l'Infarctus du Myocarde (ECTIM) Study. Hypertension 28: 881-887.
- Cantor MJ, Nickerson P, Bernstein CN (2005) The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol 100: 1134-1142.
- Coll E, Cormand B, Campos B, González-Núñez D, Iñigo P, Botey A, Poch E (2004) Association of TGF-beta1 polymorphisms with chronic renal disease. J Nephrol 17: 794-799.
- Cotton SA, Gbadegesin RA, Williams S, Brenchley PE, Webb NJ (2002) Role of TGF-beta1 in renal parenchymal scarring following childhood urinary tract infection. Kidney Int 61: 61-67.
- Derynck R, Rhee L, Chen EY, Van Tilburg A (1987) Intron-exon structure of the human transforming growth factor-β1precursor gene. Nucleic Acids Res 15: 3188-3189.
- Drumm ML, Konstan MW, Schluchter MD, Handler A, Pace R, Zou F, Zariwala M, Fargo D, Xu A, Dunn JM, Darrah RJ, Dorfman R, Sandford AJ, Corey M, Zielenski J, Durie P, Goddard K, Yankaskas JR, Wright FA, Knowles MR (2005) Gene Modifier Study Group. Genetic modifiers of lung disease in cystic fibrosis. N Engl J Med 353: 1443-1453.
- Fiocchi C (1998) Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology 115: 182-205.
- García-González MA, Crusius JBA, Strunk MHP, Bouma G, Pérez-Centeno CM, Pals G, Meuwissen SGM, Peña AS (2000) TGFB1 gene polymorphisms and inflamatory bowel disease. Immunogenetics 51: 869-872.
- Gewaltig J, Mangasser-Stephan K, Gartung C, Biesterfeld S, Gressner AM (2002) Association of polymorphisms of the transforming growth factor-beta1 gene with the rate of progression of HCV-induced liver fibrosis. Clin Chim Acta 316: 83-94.
- Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC, Carter ND, Spector TD (1999) Genetic control of the circulating concentration of transforming growth factor type beta1. Hum Mol Genet 8: 93-97.
- Hume GE, Fowler EV, Lincoln D, Eri R, Templeton D, Florin TH, Cavanaugh JA, Radford-Smith GL (2006) Angiotensinogen and transforming growth factor beta1: novel genes in the pathogenesis of Crohn's disease. J Med Genet 43: e51.
- Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Grand RJ, Boyle JT et al (1991) Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 12: 439-447.
- IBD Working Group of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (2005) Inflammatory bowel disease in children and adolescents: recommendations for diagnosis - the Porto criteria. J Pediatr Gastroenterol Nutr 41: 1-7.
- Kim YJ, Lee HS, Im JP, Min BH, Kim HD, Jeong JB, Yoon JH, Kim CY, Kim MS, Kim JY, Jung JH, Kim LH, Park BL, Shin HD (2003) Association of transforming growth factor-beta1 gene polymorphisms with a hepatocellular carcinoma risk in patients with chronic hepatitis B virus infection. Exp Mol Med 35: 196-202.
- Langdahl BL, Knudsen JY, Jensen HK, Gregersen N, Eriksen EF (1997) A sequence variation: 713-8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women. Bone 20: 289-294.
- Lee-Chen GJ, Liu KP, Lai YC, Juang HS, Huang SY, Lin CY (2004) Significance of the tissue kallikrein promoter and transforming growth factor-beta1 polymorphisms with renal progression in children with vesicoureteral reflux. Kidney Int 65: 1467-1472.
- Mak JC, Leung HC, Ho SP, Law BK, Ho AS, Lam WK, Ip MS, Chan-Yeung MM (2006) Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma. J Allergy Clin Immunol 117: 92-96.
- Osterreicher CH, Datz C, Stickel F, Hellerbrand C, Penz M, Hofer H, Wrba F, Penner E, Schuppan D, Ferenci P (2005) TGF-beta1 codon 25 gene polymorphism is associated with cirrhosis in patients with hereditary hemochromatosis. Cytokine 31: 142-148.
- Park BL, Han IK, Lee HS, Kim LH, Kim SJ, Shin HD (2003) Identification of novel variants in transforming growth factor-beta 1 (TGFB1) gene and association analysis with bone mineral density. Hum Mutat 22: 257-258.
- Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL (1996) A critical role for transforming growth factor-beta but not interleukin 4 in the suppression of T helper type 1-mediated colitis by CD45RB(low) CD4+T cells. J Exp Med 183: 2669-2674.
- Schulte C, Goebell H, Röher HD, Schulte KM (2001) C-509T polymorphism in the TGFB1 gene promoter: impact on Crohn's disease susceptibility and clinical parameters? Immunogenetics 53: 178-182.
- Stanisławowski M, Wierzbicki PM, Gołąb A, Adrych K, Kartanowicz D, Wypych J, Godlewski J, Smoczyński M, Kmieć Z (2009) Decreased Toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients. J Physiol Pharmacol 60 (Suppl 4): 71-75.
- Suzuki S, Tanaka Y, Orito E, Sugauchi F, Hasegawa I, Sakurai M, Fujiwara K, Ohno T, Ueda R, Mizokami M (2003) Transforming growth factor-beta-1 genetic polymorphism in Japanese patients with chronic hepatitis C virus infection. J Gastroenterol Hepatol 18: 1139-1143.
- Syrris P, Carter ND, Metcalfe JC, Kemp PR, Grainger DJ, Kaski JC, Crossman DC, Francis SE, Gunn J, Jeffery S, Heathcote K (1998) Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci 95: 659-667.
- Tamizifar B, Bagheri-Lankarani K, Naeemi S, Rismankar-Zadeh M, Taghavi A, Ghaderi A (2007) Polymorphism of the promoter region of C-509T of transforming growth factor-beta1 gene and ulcerative colitis. Arch Iran Med 10: 171-175.
- Tamizifar B, Lankarani KB, Naeimi S, Rismankar Zadeh M, Taghavi A, Ghaderi A (2008) Promoter polymorphism of transforming growth factor-β1 gene and ulcerative colitis. World J Gastroenterol 14: 243-247.
- Truelove SC, Witts LJ (1954) Cortisone in ulcerative colitis; preliminary report on a therapeutic trial. Br Med J 2: 375-378.
- Vidigal PG, Germer JJ, Zein NN (2002) Polymorphisms in the interleukin-10, tumor necrosis factor-alpha, and transforming growth factor-beta1 genes in chronic hepatitis C patients treated with interferon and ribavirin. J Hepatol 36: 271-277.
- Wierzbicki PM, Adrych K, Kartanowicz D, Wypych J, Stanislawowski M, Zwolinska-Wcislo M, Celinski K, Skrodzka D, Godlewski J, Korybalski B, Smoczynski M, Kmiec Z (2009) Overexpression of the fragile histidine triad (FHIT) gene in inflammatory bowel disease. J Physiol Pharmacol 60 Suppl 4: 57-62.
- Yang YH, Lai HJ, Kao CK, Lin YT, Chiang BL (2004) The association between transforming growth factor-beta gene promoter C-509T polymorphism and Chinese children with Henoch-Schönlein purpura. Pediatr Nephrol 19: 972-975.
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