ARTICLE INFO

Article Type

Original Research

Authors

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, Iran
Phone: +982188964792
Fax: +982188966310
tghazanfari@yahoo.com

Article History

Received:  July  1, 2014
Accepted:  August 25, 2014
ePublished:  November 6, 2014

BRIEF TEXT


… [1, 2] Mustard gas generally makes complications through alkylating potential of the cell components like RNA, DNA, proteins, and lipid membrane, leading to cell damages in genetic and metabolic levels [3]. … [4, 5] Respiratory complications are of the most important long-term complications of mustard gas [6]. Chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, increased airway response, and pulmonary fibrosis have been reported as the most common delayed pulmonary complications [7]. However, obstructive bronchitis is the most common pulmonary disease among Iranian chemically-injured victims [8]. … [9-19] TGF-β family has 3 isoforms, including TGF-β1, TGF-β2, TGF-β3, with high structural and functional similarities. TGF-β1 is the most frequent isoform and its initial sequence is highly conserved throughout evolution [20]. In human being, TGF-β1 is located on chromosome 19q and many polymorphisms have been identified in this gene [19, 21, 22].

There are different levels of pulmonary complications (mild, moderate, and severe), as well as no pulmonary complications, in 372 chemically-injured victims of Sardasht, Iran [9]. The serum level of 1/CCL2 MCP factors has increased and CCL5, IL-8/CXCL8, and RANTES have decreased in the victims [10]. IL-1β, IL-1α, IL-1Ra, and TNF have decreased in the chemically-injured victims of Sardasht [11]. In addition, the serum levels of soluble P-, E-, and L-selectins (of inflammatory mediators) have changed with reduced P and L and increased E [12]. There is a correlation between increase in TGF-β1 and delayed pulmonary complications in chemically-injured victims [13-16]. Some polymorphisms of TGF-β1 gene affect its expression [23]. There are correlations between some genotypes and chronic inflammatory diseases of the lung [21, 26]. In the promoter region, polymorphism leads to changes in the regulation of gene transcription and therefore, affects progression and severity of TGF-β1 diseases [19]. There is a significant correlation between C→T transition in -509 promoter region of TGF-β1 and plasma concentration of TGF-β1 [27]. TGF-β1 gene polymorphism might affect increase in its serum level that leads to more sever pulmonary complications.

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 victims.

This is a cohort study.

252 chemically-injured veterans of Sardasht City (Iran) were studied.

Definitive exposure to sulfur mustard at June 1987 (based on the veterans’ medical records), male sex, the age between 20 to 60 years, and no use of immunosuppressive medication in the month leading up to the sampling were inclusion criteria to the study. Systemic disease before exposure to sulfur mustard (based on medical records) and defects in the records of Pulmonology were non-inclusion criteria. Based on the inclusion criteria, 107 chemically-injured veterans with pulmonary complications and 145 persons without pulmonary complications were studied.

Age, body mass index (BMI), marital status, and smoking background were included in the demographic questionnaire. After full pulmonary examinations done by pulmonary specialists via interviews and examinations, the professional questionnaires of pulmonary examinations were completed. Under close supervision of a team of experienced nurses, spirometry was done based on criteria of the American Thoracic Society (1995), using spirometer device (Chest801; Japan). Peripheral blood samples were collected in the tubes containing EDTA.Genomic DNA was extracted from peripheral blood leukocytes, using kite (DNG TM-Plus; CinnaGen).PCR reaction was done in 20µl final volume using primer (TIB MOLBIOL; Germany) (Table 1). PCR-RFLP method was used to determine genotype of the subjects. The PCR productions of -509 region were digested usingEco81 I limiting enzyme (Thermo Scientific; USA).In order to detect fragments of enzymatic digestion, the productions were electrophoresed on 2.5-3.5% agarose gel. Statistical analyses were done using SPSS 18 software. The frequency of the alleles was determined via allele counting method. Genotype comparison in the groups was done, using Chi-square test.

No significant difference was observed between genotype distribution of the polymorphism of C→T in -509 promoter region of TGF-β1 gene and frequency of the related alleles in the groups with and without pulmonary complications (Table 2).

… [28, 29] Regarding genotype distribution of C→T polymorphism in -509 region of TGF-β1 gene and frequency of the related alleles, there was no significant difference between the groups with and without pulmonary complications. There is still no study about TGF-β1 polymorphism in the chemically-injured victims. There has been significant difference between TGF-β1 plasma levels in chronic obstructive pulmonary disease group and control group, while there has been no significant difference in genotype distribution and allele frequency between the groups. It has been suggested that high TGF-β1 plasma level may play a role in pathogenesis of chronic obstructive pulmonary disease. C→T polymorphism in -509 region and T→C in +869 region of TGF-β1 gene have not shown genetic susceptibility to chronic obstructive pulmonary disease in the Chinese [30], which is consistent with the present results. Frequency of T allele in -509 region in control group has been significantly higher than peoples with chronic obstructive pulmonary disease. In addition, frequency of A allele in -800 region in peoples with chronic obstructive pulmonary disease has been significantly higher than control group, which may show probable role of promoter polymorphism of TGF-β1 gene in chronic obstructive pulmonary disease [20]. … [31]

Regarding polymorphism in other regions of promoter, changes in other regions such as G→A polymorphism in -800 region, and their relations to the long-term pulmonary complications ought to be investigated. The correlations between the genotypes and other long-term complications of sulfur mustard (including ocular and cutaneous complications) ought to be studied.

Non-declared

There is no correlation between long-term pulmonary complications of sulfur mustard and C→T polymorphism in -509 promoter region of TGF-β1 gene.

The researchers feel grateful to all the participants.

Non-declared

All the procedures were approved by Ethics Committee of Janbazan Medical and Engineering Research Center and Research Council of Shahed University.

The study was funded by Shahed University, Martyrs and Veterans Foundation, and Janbazan Medical and Engineering Research Center.

TABLES and CHARTS

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CITIATION LINKS

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