TGF- 1 Variants in Chronic Beryllium Disease and Sarcoidosis

Robert H. Hollis Laboratory of Environmental and Occupational Health, Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA.
The Journal of Immunology (Impact Factor: 4.92). 10/2007; 179(6):4255-62. DOI: 10.4049/jimmunol.179.6.4255
Source: PubMed


Evidence suggests a genetic predisposition to chronic beryllium disease (CBD) and sarcoidosis, which are clinically and pathologically similar granulomatous lung diseases. TGF-beta1, a cytokine involved in mediating the fibrotic/Th1 response, has several genetic variants which might predispose individuals to these lung diseases. We examined whether certain TGF-beta1 variants and haplotypes are found at higher rates in CBD and sarcoidosis cases compared with controls and are associated with disease severity indicators for both diseases. Using DNA from sarcoidosis cases/controls from A Case Control Etiologic Study of Sarcoidosis Group (ACCESS) and CBD cases/controls, TGF-beta1 variants were analyzed by sequence-specific primer PCR. No significant differences were found between cases and controls for either disease in the TGF-beta1 variants or haplotypes. The -509C and codon 10T were significantly associated with disease severity indicators in both CBD and sarcoidosis. Haplotypes that included the -509C and codon 10T were also associated with more severe disease, whereas one or more copies of the haplotype containing the -509T and codon 10C was protective against severe disease for both sarcoidosis and CBD. These studies suggest that the -509C and codon 10T, implicated in lower levels of TGF-beta1 protein production, are shared susceptibility factors associated with more severe granulomatous disease in sarcoidosis and CBD. This association may be due to lack of down-regulation by TGF-beta1, although future studies will be needed to correlate TGF-beta1 protein levels with known TGF-beta1 genotypes and assess whether there is a shared mechanisms for TGF-beta1 in these two granulomatous diseases.

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Available from: Lee Newman, Oct 28, 2015
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    • ". TGFβ 1 has an immunoregulatory role in decreasing granulomatous inflammation [39] [40], but abnormally increased levels induce fibroblast collagen synthesis leading to fibrosis [41] [42]. One other study was unable to show a correlation between BAL and EBC TGF-β 1 levels in patients with sarcoidosis [10]. "
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    Journal of Breath Research 10/2013; 7(4):046003. · 4.63 Impact Factor
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    • "In some studies, the allele 2 frequency of IL1RN was increased in inflammatory diseases such as ulcerative colitis, silicosis and dementia [Mansfield et al., 1994; Yucesoy et al., 2001, 2005], respectively. Several studies have also reported an increase of TGFB1 allele 2 frequency in some diseases such as cystic fibrosis, and systemic sclerosis and sarcoidosis compared to controls [Arkwright et al., 2000; Ohtsuka et al., 2002; Jonth et al., 2007]. Similarly, in line with these observations, we found that the frequencies of allele 2 for both IL1RN and TGFB1, were increased in development and severity of CWP. "
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    ABSTRACT: Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). An additional goal was to observe whether these cytokine gene polymorphisms influence the development risk and severity of. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TNFA (-238) gene polymorphism principally affected CWP development and severity (OR = 3.47: 95% CI, 1.12-10.77 and OR = 4.30: 95% CI, 1.25-14.74, respectively) and also risk of CWP (OR = 3.79: 95% CI, 1.37-10.46). The TNFA (-308) variant was associated with a risk for the CWP severity (OR = 2.84: 95% CI, 1.08-7.39). A protective effect of IL6 was found on the development (OR = 0.48: 95% CI, 0.21-0.93) and severity of CWP (OR = 0.37: 95% CI, 0.15-0.91). We suggest that TNFA (-238) variant may be a risk factor in both development and the severity of CWP, while TNFA (-308) variant seems to be important only in disease severity. On the other hand, IL6 variant may have a protective effect on the development and disease severity.
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