Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2016, vol. 25, nr 2, March-April, p. 273–278

doi: 10.17219/acem/32211

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

TGFB1 Gene Promoter Polymorphisms in Serbian Asthmatics

Sandra Dragicevic1,A,B,C,D,E,F, Natasa Petrovic-Stanojevic2,A,B,C,D,E,F, Aleksandra Nikolic1,A,B,C,D,E,F

1 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia

2 Department of Pulmonology, Zvezdara University Medical Center, Belgrade, Serbia

Abstract

Background. Asthma is a chronic respiratory disease caused by a combination of genetic and environmental factors. Transforming growth factor beta 1 (TGFB1) is a multifunctional cytokine that plays an important role in airway remodeling in asthma.
Objectives. The aim of this study was to analyze common TGFB1 gene promoter polymorphisms C-509T and G-800A in Serbian asthmatics and to investigate their association with exacerbations.
Material and Methods. The study involved 102 asthmatics and 58 healthy individuals from Serbia, age and gender matched. An analysis of the TGFB1 promoter was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results. For polymorphism C-509T a significant difference in the allele frequency was observed between the patients and the controls (p = 0.011), while the genotype distribution was similar in the analyzed groups, with statistical significance near the borderline (p = 0.061). For the polymorphism G-800A no difference was observed between the groups. The frequency of the -509TT genotype was higher in patients with exacerbations compared to patients without exacerbations (36.4% vs. 17.0%), with statistical significance near the borderline (p = 0.080).
Conclusion. The results suggest that polymorphism C-509T may be associated with asthma and disease exacerbations, while G-800A is not significant for the etiology and clinical course of the disease. These findings should be confirmed in a larger study group, and since the TGFB1 promoter is highly complex and very responsive to environmental factors, future studies should also take other genetic and non-genetic factors into consideration.

Key words

asthma, gene polymorphism, transforming growth factor beta 1

References (29)

  1. Postma DS, Timens W: Remodeling in asthma and chronic obstructive pulmonary disease. Proc Am Thorac Soc 2006, 3, 434–439.
  2. Bartram U, Speer CP: The role of transforming growth factor beta in lung development and disease. Chest 2004, 125, 754–765.
  3. Lv J, Liu Q, Hua L, Dong X, Bao Y: Association of five single nucleotide polymorphism loci with asthma in children of Chinese Han nationality. J Asthma 2009, 46, 582–585.
  4. Weiss ST, Raby BA, Rogers A: Asthma genetics and genomics. Curr Opin Genet Dev 2009, 19, 279–282.
  5. Kumar A, Ghosh B: Genetics of asthma: A molecular biologist perspective. Clin Mol Allergy 2009, 7, 7.
  6. Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma 2014.
  7. Wu L, Chau J, Young RP, Pokorny V, Mills GD, Hopkins R: Transforming growth factor-beta1 genotype and susceptibility to chronic obstructive pulmonary disease. Thorax 2004, 59, 126–129.
  8. Howell JE, McAnulty RJ: TGF-beta: its role in asthma and therapeutic potential. Curr Drug Targets 2006, 7, 547–565.
  9. Bossé Y, Rola-Pleszczynski M: Controversy surrounding the increased expression of TGF beta 1 in asthma. Respir Res 2007, 8, 66.
  10. Duvernelle C, Freund V, Frossard N: Transforming growth factor-beta and its role in asthma. Pulm Pharmacol Ther 2003, 16, 181–196.
  11. Eap R, Jacques E, Semlali A, Plante S, Chakir J: Cysteinyl leukotrienes regulate TGF-β(1) and collagen production by bronchial fibroblasts obtained from asthmatic subjects. Prostaglandins Leukot Essent Fatty Acids 2012, 86, 127–133.
  12. Shah R, Rahaman B, Hurley CK, Posch PE: Allelic diversity in the TGFB1 regulatory region: Characterization of novel functional single nucleotide polymorphisms. Hum Genet 2006, 119, 61–74.
  13. Tamizifar B, Lankarani KB, Naeimi S, Rismankar Zadeh M, Taghavi A, Ghaderi A: Promoter polymorphism of transforming growth factor-beta1 gene and ulcerative colitis. World J Gastroenterol 2008, 14, 243–247.
  14. Schulte CM, Goebell H, Röher HD, Schulte KM: C-509T polymorphism in the TGFB1 gene promoter: Impact on Crohn’s disease susceptibility and clinical course? Immunogenetics 2001, 53, 178–182.
  15. Silverman ES, Palmer LJ, Subramaniam V, Hallock A, Mathew S, Vallone J: Transforming growth factor-beta1 promoter polymorphism C-509T is associated with asthma. Am J Respir Crit Care Med 2004, 169, 214–219.
  16. Ueda T, Niimi A, Matsumoto H, Takemura M, Yamaguchi M, Matsuoka H: TGFB1 promoter polymorphism C-509T and pathophysiology of asthma. J Allergy Clin Immunol 2008, 121, 659–664.
  17. Nagpal K, Sharma S, B-Rao C, Nahid S, Niphadkar PV, Sharma SK: TGFbeta1 haplotypes and asthma in Indian populations. J Allergy Clin Immunol 2005, 115, 527–533.
  18. Syrris P, Carter ND, Metcalfe JC, Kemp PR, Grainger DJ, Kaski JC: Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. Clin Sci (Lond) 1998, 95, 659–667.
  19. Wiśniewski A, Obojski A, Pawlik A, Jasek M, Luszczek W, Majorczyk E: Polymorphism of the TGFB1 gene is not associated with bronchial allergic asthma in a Polish population. Hum Immunol 2009, 70, 134–138.
  20. Saltzman BS, Yamamoto JF, Decker R, Yokochi L, Theriault AG, Vogt TM: Association of genetic variation in the transforming growth factor beta-1 gene with serum levels and risk of colorectal neoplasia. Cancer Res 2008, 68, 1236–1244.
  21. Yang YC, Zhang N, Van Crombruggen K, Hu GH, Hong SL, Bachert C: Transforming growth factor-beta1 in inflammatory airway disease: a key for understanding inflammation and remodeling. Allergy 2012, 67, 1193–1202.
  22. Li H, Romieu I, Wu H, Sienra-Monge JJ, Ramírez-Aguilar M, del Río-Navarro BE: Genetic polymorphisms in transforming growth factor beta-1 (TGFB1) and childhood asthma and atopy. Hum Genet 2007, 121, 529–538.
  23. Pulleyn LJ, Newton R, Adcock IM, Barnes PJ: TGFbeta1 allele association with asthma severity. Hum Genet 2001, 109, 623–627.
  24. Salam MT, Gauderman WJ, McConnell R, Lin PC, Gilliland FD: Transforming growth factor-1 C-509T polymorphism, oxidant stress, and early-onset childhood asthma. Am J Respir Crit Care Med 2007, 176, 1192–1199.
  25. Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L: Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med 1998, 158, 1958–1962.
  26. Buckova D, Izakovicová Hollá L, Benes P, Znojil V, Vácha J: TGF-beta1 gene polymorphisms. Allergy 2001, 56, 1236–1237.
  27. Heinzmann A, Bauer E, Ganter K, Kurz T, Deichmann KA: Polymorphisms of the TGF-beta1 gene are not associated with bronchial asthma in Caucasian children. Pediatr Allergy Immunol 2005, 16, 310–314.
  28. Mak JC, Leung HC, Ho SP, Law BK, Ho AS, Lam WK: Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma. J Allergy Clin Immunol 2006, 117, 92–96.
  29. Acevedo N, Vergara C, Gusmão L, Jiménez S, Martínez B, Mercado D: The C-509T promoter polymorphism of the transforming growth factor beta-1 gene is associated with levels of total and specific IgE in a Colombian population. Int Arch Allergy Immunol 2010, 151, 237–246.