Association of transforming growth factor-β1 gene variants with risk of coal workers' pneumoconiosis

Abstract

ObjectiveThe 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).MethodsThe 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.ResultsThe 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.ConclusionThis study suggests that TGF-β1 polymorphisms may contribute to susceptibility of CWP.

Association between Genetic Variants of Transforming Growth Factor-β1 and Susceptibility of Pneumoconiosis

“…The study selection process is shown in Figure 1 . Seven of these studies investigated association between TGF-β1 −509 C>T polymorphism and pneumoconiosis,[ 15 16 17 18 19 20 21 ] nine involved +869 T>C polymorphism,[ 15 17 18 19 20 22 23 24 25 ] and five involved +915 G>C polymorphism. [ 15 17 19 20 24 ] The characteristics of each selected study are listed in Tables 1 – 3 .…”

“…Specifically, Table 1 shows characteristics of case and control for association of −509 C>T polymorphism with pneumoconiosis, six of which were performed in Asia. [ 15 17 18 19 20 21 ] One was performed in Caucasus,[ 16 ] originating from China and USA, respectively. Pneumoconiosis was induced by coal in two studies, and others were induced by silicosis.…”

“…[ 14 ] Several polymorphic variants in TGF-β1 , such as −509 C>T (rs1800469), +869 T>C (rs1800470), and +915 G>C (rs1800471), were assessed for association with pneumoconiosis risk, the data remain controversial currently. [ 15 16 17 18 19 20 21 22 23 24 25 ] In 2012, a meta-analysis published in Chinese reported that TGF-β1 gene −509 C>T, +869 T>C polymorphisms were not associated with risk of developing pneumoconiosis. [ 26 ] However, only small sample size related to TGF-β1 gene −509 C>T, +869 T>C was involved in this meta-analysis, and thus, it was unable to provide enough persuasiveness.…”

Biomarkers for Pulmonary Inflammation and Fibrosis and Lung Ventilation Function in Chinese Occupational Refractory Ceramic Fibers-Exposed Workers

“…There are some sensitive biomarkers, including transforming growth factor-β1 (TGF-β1) and ceruloplasmin (CP), which had been found able to detect the pulmonary inflammation and fibrosis induced by occupational exposure to asbestos or other toxicants. TGF-β1 is a multifunctional cytokine that is critically involved in the pathogenesis of fibrosis and contributes to the influx and activation of inflammatory cells [ 13 , 14 ]. Previous studies found that TGF-β1 plays a key role in the development of lung fibrosis, and the expression of TGF-β1 increases in lung tissue of patients with lung fibrosis and animal models of pulmonary fibrosis [ 15 , 16 , 17 ].…”

GITR promoter polymorphism contributes to risk of coal workers’ pneumoconiosis: A case–control study from China

“…prolonged lung inflammation and fibrotic nodular lesions that usually lead to progressive fibrosis [5]. Although silica dust exposure is recognized as the primary cause of pneumoconiosis, extensive researches indicate that genetic factors have played important roles in the development of pulmonary fibrosis [2,[6][7][8]. During the past four decades in China, CWP continues to occur even though work environment and prevention measures have been greatly improved [9], and still more than 23 million workers exposed to silica particles [10].…”