@2024 Afarand., IRAN
ISSN: 2008-2630 Iranian Journal of War & Public Health 2014;6(5):221-226
ISSN: 2008-2630 Iranian Journal of War & Public Health 2014;6(5):221-226
Correlation of C→T Polymorphism in -509 Promoter Region of TGF-β1 Gene with Long-Term Pulmonary Complications in Sulfur Mustard Chemical Injures
ARTICLE INFO
Article Type
Original ResearchAuthors
Mohammadi M (1)Ghazanfari T (*)
Amani D (2)
Naghizadeh M.M (3)
(*) Immunoregulation Research Center, Shahed University, Tehran, Iran
(1) Immunology Department, Medicine Faculty, Shahed University, Tehran, Iran
(2) Immunology Department, Medicine Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
(3) Biostatistics Department, Medicine Faculty, Fasa University of Medical Sciences, Fasa, Iran
Correspondence
Address: No. 21, Medicine Faculty, Shahed University, Shahid Abdollahzade Street, Keshavarz Boulevard, Tehran, IranPhone: +982188964792
Fax: +982188966310
tghazanfari@yahoo.com
Article History
Received: July 1, 2014Accepted: August 25, 2014
ePublished: November 6, 2014
ABSTRACT
Aims
Sulfur mustard causes blister and was used for the first time as a chemical weapon in
World War I and during the Iran-Iraq war as well. The aim of this study was to investigate the
correlation of C→T polymorphism in -509 promoter region of TGF-β1 gene with long-term
pulmonary complications in sulfur mustard chemical injures.
Materials & Methods This study was done on 252 chemically-injured veterans including 107 exposed subjects with pulmonary problems and 145 subjects without pulmonary problems. Peripheral blood samples were collected in the tubes containing EDTA. Then, genomic DNA was extracted of peripheral blood leukocytes. PCR-RFLP method was used to determine genotype of the subjects. Statistical analysis was done using SPSS 18 by Chi-square test.
Findings 33 subjects in chemically-injured patients with pulmonary problems group and 43 subjects in groups without pulmonary problems had CC homozygous genotype. 59 chemically-injured patients with pulmonary problems and 76 subjects of the group without pulmonary problems had CT heterozygous genotype (p=0.967). Also, 15 subjects of pulmonary problems group and 26 subjects of the group without pulmonary problems had TT homozygous genotype (p=0.473). No significant difference was observed between different genotype distribution of the polymorphism of C→T in -509 promoter region of TGF-β1 gene of with and without pulmonary problem groups.
Conclusion C→T polymorphism in -509 promoter region of TGF-β1 gene is not correlated with pulmonary problems in chemical injured veterans.
Materials & Methods This study was done on 252 chemically-injured veterans including 107 exposed subjects with pulmonary problems and 145 subjects without pulmonary problems. Peripheral blood samples were collected in the tubes containing EDTA. Then, genomic DNA was extracted of peripheral blood leukocytes. PCR-RFLP method was used to determine genotype of the subjects. Statistical analysis was done using SPSS 18 by Chi-square test.
Findings 33 subjects in chemically-injured patients with pulmonary problems group and 43 subjects in groups without pulmonary problems had CC homozygous genotype. 59 chemically-injured patients with pulmonary problems and 76 subjects of the group without pulmonary problems had CT heterozygous genotype (p=0.967). Also, 15 subjects of pulmonary problems group and 26 subjects of the group without pulmonary problems had TT homozygous genotype (p=0.473). No significant difference was observed between different genotype distribution of the polymorphism of C→T in -509 promoter region of TGF-β1 gene of with and without pulmonary problem groups.
Conclusion C→T polymorphism in -509 promoter region of TGF-β1 gene is not correlated with pulmonary problems in chemical injured veterans.
CITATION LINKS
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[2]Ghazanfari T, Mohammad Hassan Z, Foroutan A. The long-term consequences of sulfur mustard on Iranian chemical victims: Introduction. Toxin Rev. 2009;28(1):1-2.
[3]Kehe K, Szinicz L. Medical aspects of sulphur mustard poisoning. Toxicology. 2005;214(3):198-209.
[4]Parvizpour F, Ghazanfari T, Salimi H, Faghihzadeh S,Yaraee R, Sharifnia Z, et al. NFκB gene expression survey in peripheral blood cell of Sardasht Warfare Agent victims 20 years after exposure to sulfur mustard. Iran J War Pub Health. 2011;3(12):38-47.
[5]Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL. Sulfur mustard-induced pulmonary injury: therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther. 2011;24(1):92-9.
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[7]Lari SM, Attaran D, Towhidi M. COPD due to sulfur mustard (mustard lung). Available from: http://cdn.intechopen.com/pdfs-wm/30169.pdf.
[8]Ghanei M, Fathi H, Mohammad MM, Aslani J, Nematizadeh F. Long-term respiratory disorders of claimers with subclinical exposure to chemical warfare agents. Inhal Toxicol. 2004;16(8):491-5.
[9]Ghazanfari T, Faghihzadeh S, Aragizadeh H, Soroush MR, Yaraee R, Mohammad Hassan Z, et al. Sardasht-Iran cohort study of chemical warfare victims: Design and methods. Arch Iran Med. 2009;12(1):5-14.
[10]Ghazanfari T, Yaraee R, Kariminia A, Ebtekar M, Faghihzadeh S, Vaez-Mahdavi MR, et al. Alterations in the serum levels of chemokines 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1471-6
[11]Yaraee R, Ghazanfari T, Ebtekar M, Ardestani SK, Rezaei A, Kariminia A, et al. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. Int Immunopharmacol. 2009;9(13-14):1466-70.
[12]Yaraee R, Ghazanfari T, Faghihzadeh S, Mostafaie A, Soroush MR, Inai K, et al. Alterations in the serum levels of soluble L, P and E-selectin 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1477-81.
[13]Emad A, Emad Y. Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J Interferon Cytokine Res. 2007;27(1):38-43.
[14]Arzan Zarin A, Behmanesh M, Tavallaei M, Shohrati M, Ghanei M. Overexpression of transforming growth factor (TGF)-β1 and TGF-β3 genes in lung of toxic-inhaled patients. Exp Lung Res. 2010;36(5):284-91.
[15]Aghanouri R, Ghanei M, Aslani J, Keivani-Amine H, Rastegar F, Karkhane A. Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard. Am J Physiol Lung Cell Mol Physiol. 2004;287(6):L1160-4
[16]Mirzamani MS, Nourani MR, Imani Fooladi AA, Zare S, Ebrahimi M, Yazdani S, et al. Increased expression of transforming growth factor-β and receptors in primary human airway fibroblasts from chemical inhalation patients. Iran J Allergy Asthma Immunol. 2013;12(2):144-52.
[17]Grainger DJ, Mosedale DE, Metcalfe JC. TGF-β in blood: A complex problem. Cytokine Growth Factor Rev. 2000;11(1-2):133-45.
[18]Tamizifar B, Bagheri-Lankarani K, Naeemi S, Rismankar-Zadeh M, Taghavi A, Ghaderi A. Polymorphism of the promoter region of C-509T of transforming growth factor-beta1 gene and ulcerative colitis. Arch Iran Med. 2007;10(2):171-5.
[19]Amani D, Zolghadri J, Samsami Dehaghani A, Pezeshki AM, Ghaderi A. The promoter region (− 800,− 509) polymorphisms of transforming growth factor-β1 (TGF-β1) gene and recurrent spontaneous abortion. J Reprod Immunol. 2004;62(1-2):159-66.
[20]Su ZG, Wen FQ, Feng YL, Xiao M, Wu XL. Transforming growth factor-β1 gene polymorphisms associated with chronic obstructive pulmonary disease in Chinese population. Acta Pharmacologica Sinica. 2005;26(6):714-20.
[21]Hersh CP, Demeo DL, Lazarus R, Celedón JC, Raby BA, Benditt JO, et al. Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173(9):977-84.
[22]Xaubet A, Marin-Arguedas A, Lario S, Ancochea J, Morell F, Ruiz-Manzano J, et al. Transforming growth factor-β1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168(4):431-5.
[23]Liu DS, Li XO, Ying BW, Chen L, Wang T, Xu D, Wen, et al. Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese. Chin Med J. 2010;123(4):390-4.
[24]Wu L, Chau J, Young R, Pokorny V, Mills G, Hopkins R, et al. Transforming growth factor-β1 genotype and susceptibility to chronic obstructive pulmonary disease. Thorax. 2004;59(2):126-9.
[25]Celedón JC, Lange C, Raby BA, Litonjua AA, Palmer LJ, DeMeo DL, et al. The transforming growth factor-β1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD). Hum Mol Genet. 2004;13(15):1649-56.
[26]Ito M, Hanaoka M, Droma Y, Hatayama O, Sato E, Katsuyama Y, et al. The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese. Intern Med. 2008;47(15):1387-94
[27]Caserta TM, Knisley AA, Tan FK, Arnett FC, Brown TL. Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus erythematosus and Sjogren's syndrome. Ann Genet. 2004;47(4):359-63.
[28]Graham JS, Chilcott RP, Rice P, Milner SM, Hurst CG, Maliner BI. Wound healing of cutaneous sulfur mustard injuries: strategies for the development of improved therapies. J Burns Wounds. 2005;4:e1.
[29]Khateri Sh, Ghanei M, Keshavarz S, Soroush M, Haines D. Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. J Occup Environ Med. 2003;45(11):1136-43.
[30]Mak JC, Chan-Yeung MM, Ho SP, Chan KS, Choo K, Yee KS, et al. Elevated plasma TGF-β1 levels in patients with chronic obstructive pulmonary disease. Respir Med. 2009;103(7):1083-9.
[31]Snyder LD, Hartwig MG, Ganous T, Davis RD, Herczyk WF, Reinsmoen NL, et al. Cytokine gene polymorphisms are not associated with bronchiolitis obliterans syndrome or survival after lung transplant. J Heart Lung Transplant. 2006;25(11):1330-5.
[2]Ghazanfari T, Mohammad Hassan Z, Foroutan A. The long-term consequences of sulfur mustard on Iranian chemical victims: Introduction. Toxin Rev. 2009;28(1):1-2.
[3]Kehe K, Szinicz L. Medical aspects of sulphur mustard poisoning. Toxicology. 2005;214(3):198-209.
[4]Parvizpour F, Ghazanfari T, Salimi H, Faghihzadeh S,Yaraee R, Sharifnia Z, et al. NFκB gene expression survey in peripheral blood cell of Sardasht Warfare Agent victims 20 years after exposure to sulfur mustard. Iran J War Pub Health. 2011;3(12):38-47.
[5]Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL. Sulfur mustard-induced pulmonary injury: therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther. 2011;24(1):92-9.
[6]Pourfarzam S, Ghazanfari T, Merasizadeh J, Ghanei M, Azimi G, Araghizadeh H, et al. Long-term pulmonary complications in sulfur mustard victims of Sardasht, Iran. Toxin Rev. 2009;28(1):8-13.
[7]Lari SM, Attaran D, Towhidi M. COPD due to sulfur mustard (mustard lung). Available from: http://cdn.intechopen.com/pdfs-wm/30169.pdf.
[8]Ghanei M, Fathi H, Mohammad MM, Aslani J, Nematizadeh F. Long-term respiratory disorders of claimers with subclinical exposure to chemical warfare agents. Inhal Toxicol. 2004;16(8):491-5.
[9]Ghazanfari T, Faghihzadeh S, Aragizadeh H, Soroush MR, Yaraee R, Mohammad Hassan Z, et al. Sardasht-Iran cohort study of chemical warfare victims: Design and methods. Arch Iran Med. 2009;12(1):5-14.
[10]Ghazanfari T, Yaraee R, Kariminia A, Ebtekar M, Faghihzadeh S, Vaez-Mahdavi MR, et al. Alterations in the serum levels of chemokines 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1471-6
[11]Yaraee R, Ghazanfari T, Ebtekar M, Ardestani SK, Rezaei A, Kariminia A, et al. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. Int Immunopharmacol. 2009;9(13-14):1466-70.
[12]Yaraee R, Ghazanfari T, Faghihzadeh S, Mostafaie A, Soroush MR, Inai K, et al. Alterations in the serum levels of soluble L, P and E-selectin 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1477-81.
[13]Emad A, Emad Y. Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. J Interferon Cytokine Res. 2007;27(1):38-43.
[14]Arzan Zarin A, Behmanesh M, Tavallaei M, Shohrati M, Ghanei M. Overexpression of transforming growth factor (TGF)-β1 and TGF-β3 genes in lung of toxic-inhaled patients. Exp Lung Res. 2010;36(5):284-91.
[15]Aghanouri R, Ghanei M, Aslani J, Keivani-Amine H, Rastegar F, Karkhane A. Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard. Am J Physiol Lung Cell Mol Physiol. 2004;287(6):L1160-4
[16]Mirzamani MS, Nourani MR, Imani Fooladi AA, Zare S, Ebrahimi M, Yazdani S, et al. Increased expression of transforming growth factor-β and receptors in primary human airway fibroblasts from chemical inhalation patients. Iran J Allergy Asthma Immunol. 2013;12(2):144-52.
[17]Grainger DJ, Mosedale DE, Metcalfe JC. TGF-β in blood: A complex problem. Cytokine Growth Factor Rev. 2000;11(1-2):133-45.
[18]Tamizifar B, Bagheri-Lankarani K, Naeemi S, Rismankar-Zadeh M, Taghavi A, Ghaderi A. Polymorphism of the promoter region of C-509T of transforming growth factor-beta1 gene and ulcerative colitis. Arch Iran Med. 2007;10(2):171-5.
[19]Amani D, Zolghadri J, Samsami Dehaghani A, Pezeshki AM, Ghaderi A. The promoter region (− 800,− 509) polymorphisms of transforming growth factor-β1 (TGF-β1) gene and recurrent spontaneous abortion. J Reprod Immunol. 2004;62(1-2):159-66.
[20]Su ZG, Wen FQ, Feng YL, Xiao M, Wu XL. Transforming growth factor-β1 gene polymorphisms associated with chronic obstructive pulmonary disease in Chinese population. Acta Pharmacologica Sinica. 2005;26(6):714-20.
[21]Hersh CP, Demeo DL, Lazarus R, Celedón JC, Raby BA, Benditt JO, et al. Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2006;173(9):977-84.
[22]Xaubet A, Marin-Arguedas A, Lario S, Ancochea J, Morell F, Ruiz-Manzano J, et al. Transforming growth factor-β1 gene polymorphisms are associated with disease progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168(4):431-5.
[23]Liu DS, Li XO, Ying BW, Chen L, Wang T, Xu D, Wen, et al. Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese. Chin Med J. 2010;123(4):390-4.
[24]Wu L, Chau J, Young R, Pokorny V, Mills G, Hopkins R, et al. Transforming growth factor-β1 genotype and susceptibility to chronic obstructive pulmonary disease. Thorax. 2004;59(2):126-9.
[25]Celedón JC, Lange C, Raby BA, Litonjua AA, Palmer LJ, DeMeo DL, et al. The transforming growth factor-β1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD). Hum Mol Genet. 2004;13(15):1649-56.
[26]Ito M, Hanaoka M, Droma Y, Hatayama O, Sato E, Katsuyama Y, et al. The association of transforming growth factor beta 1 gene polymorphisms with the emphysema phenotype of COPD in Japanese. Intern Med. 2008;47(15):1387-94
[27]Caserta TM, Knisley AA, Tan FK, Arnett FC, Brown TL. Genotypic analysis of the TGF beta-509 allele in patients with systemic lupus erythematosus and Sjogren's syndrome. Ann Genet. 2004;47(4):359-63.
[28]Graham JS, Chilcott RP, Rice P, Milner SM, Hurst CG, Maliner BI. Wound healing of cutaneous sulfur mustard injuries: strategies for the development of improved therapies. J Burns Wounds. 2005;4:e1.
[29]Khateri Sh, Ghanei M, Keshavarz S, Soroush M, Haines D. Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. J Occup Environ Med. 2003;45(11):1136-43.
[30]Mak JC, Chan-Yeung MM, Ho SP, Chan KS, Choo K, Yee KS, et al. Elevated plasma TGF-β1 levels in patients with chronic obstructive pulmonary disease. Respir Med. 2009;103(7):1083-9.
[31]Snyder LD, Hartwig MG, Ganous T, Davis RD, Herczyk WF, Reinsmoen NL, et al. Cytokine gene polymorphisms are not associated with bronchiolitis obliterans syndrome or survival after lung transplant. J Heart Lung Transplant. 2006;25(11):1330-5.