Abstract
Objective The aim of this case-control study was to explore whether five tagging single nucleotide polymorphisms (tSNPs) within the transforming growth factor-β1 ( TGF-β1) gene were involved in manifestation of inflammatory and fibrotic processes associated with coal workers' pneumoconiosis (CWP). Methods The study included 508 CWP patients and 526 controls who were underground coal miners from Xuzhou Mining Business Group. Five tSNPs were selected from the HapMap and detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results The single SNP analysis showed that the genotype frequencies of SNP2 (rs1800470, +869T/C, extron 1) and SNP5 (rs11466345, intron 5) in CWP cases were significantly different from those in controls. Multivariate logistic regression analysis revealed that SNP2 (rs1800470) CC genotype was associated with decreased risk of CWP (OR = 0.50, 95% CI = 0.32–0.78), which was evident among subgroups of those never smoke (OR = 0.40, 95%CI = 0.24–0.66), cases with stage II (OR = 0.41, 95%CI = 0.22–0.76) and exposure period (< 28 y: OR = 0.54, 95%CI = 0.31–0.95; ≥ 28 y: OR = 0.52, 95%CI = 0.32–0.96). However, the SNP5 (rs11466345) GG genotype was associated with an increased risk of CWP (OR = 2.5, 95%CI = 1.36–4.57), and further stratification analysis showed that the risk of CWP was increased in both smoking and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and II . Conclusion This study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.
Highlights
Pneumoconiosis is a global occupational health problem, especially in China with an annual incidence of nearly 80% of all occupational diseases
Multivariate logistic regression analysis revealed that the SNP2 CC genotype was associated with decreased risk of coal workers' pneumoconiosis (CWP) (OR = 0.50, 95% CI = 0.32-0.78) and the SNP5 GG genotype was associated with an increased risk of CWP (OR = 2.24, 95% CI = 1.37-3.68)
The SNP5 GG genotype was associated with an increased risk of CWP in both smoking (OR = 0.40, 95%CI = 0.24-0.66) and nonsmoking groups, shorter and longer exposure groups, while the risk of CWP was only increased in patients with stage I and II (Table 6 )
Summary
Pneumoconiosis is a global occupational health problem, especially in China with an annual incidence of nearly 80% of all occupational diseases. Inhaling respirable coal dust and silica particulates frequently develop coal workers' pneumoconiosis (CWP), a dustassociated pneumoconiosis characterized by chronic pulmonary inflammation and fibrotic nodular lesions. Understanding genetic variability, and the interaction between genetic variation and dust exposure may aid in the identification of high-risk individuals and prevent them from developing CWP. Transforming growth factor-β1 (TGF-β1) is an important multifunctional cytokine that modulates myriad cellular and tissue processes, including cell growth, differentiation, apoptosis, and inflammation and is involved in the pathogenesis of the lung fibrosis[5,6]. TGF-β 1 contributes to the influx and activation of inflammatory cells, transdifferentiation of epithelium to mesenchyme, and influx of fibroblasts and their subsequent elaboration of extracellular matrix[7,8]
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