Risk Of Coal Workers' Pneumoconiosis Research Articles

Genetic susceptibility in pneumoconiosis in China: a systematic review.

Pneumoconiosis, encompassing coal workers' pneumoconiosis (CWP), silicosis and asbestosis, is one of the most common occupational diseases in China. Previous studies revealed significant associations between genetic variations and pneumoconiosis risk among individuals in different countries. With the known variability of genetic makeup between ethnicities, susceptibility to pneumoconiosis due to genetic differences is likely to be ethnicity-specific. The present review aimed at providing a comprehensive overview on the association between genetic polymorphisms and susceptibility of pneumoconiosis, specifically among people in China. The literature search was performed in seven English and Chinese databases using keywords related to the review aim. An appraisal of the methodological quality of the included studies was conducted using the assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Forty-five studies were included in this review. Genotypes of specific genes which are associated with the risk of CWP, silicosis and asbestosis were reported. Our findings showed that genes encoding inflammatory cytokines have been examined extensively, and they demonstrated an association between these genes and pneumoconiosis risk. Gene-environment interactions in pneumoconiosis susceptibility were also reported by a number of studies. This review summarised the evidence demonstrating the association between genetic polymorphisms and pneumoconiosis susceptibility among people in China, and that various genotypes could modify their risk to develop pneumoconiosis. The findings prompt that identification of individuals at high pneumoconiosis risk through genetic screening and strategies limiting their exposure to dust could be a potential strategy for the control of this occupational disease in China.

Association between the IL-6 polymorphisms and coal workers’ pneumoconiosis in a Chinese Hui population

ObjectiveTo determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.IntroductionGenes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.MethodsWe genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.ResultsCarrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP ( p < 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects ( p > 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.ConclusionsTaking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.

Heterozygous Ins/Del genotype of the CASP8 rs3834129 polymorphism significantly decreases the risk of coal workers' pneumoconiosis in a Chinese Han population: a case-control study.

Coal workers' pneumoconiosis (CWP) is a chronic inflammatory and fibrotic pulmonary disease that involves a complex interaction of multiple environmental and genetic factors. Polymorphism, as a genetic factor, may affect the onset of the disease in susceptible populations. The present study investigated the association between the polymorphisms of six genes and CWP risk in a Chinese Han population. Six polymorphisms (CASP8 rs3834129, IL1A rs1800587, IL6 rs1800796, IL4 rs2070874, TNFA rs361525, and NLRP3 rs1539019) were examined in 222 CWP subjects and 247 dust-exposed control subjects. The CASP8 rs3834129 Ins/Del genotype significantly decreased CWP risk (p=0.040; adjusted odds ratio [OR] = 0.586; 95% confidence interval [CI] 0.367-0.935) compared with the Ins/Ins genotype. Stratification analyses revealed a significant interaction between the heterozygous Ins/Del genotype and age. Compared with the Ins/Ins + Del/Del genotype, this was particularly evident among subjects aged 41-60 (p<0.001; adjusted OR = 0.054; 95% CI 0.007-0.420) and those with an exposure time of 20-29 years (p=0.014; adjusted OR = 0.392; 95% CI 0.183-0.842). This decreased risk was also found in the group with former smokers (p=0.012; adjusted OR = 0.448; 95% CI 0.238-0.844). Findings revealed that the heterozygous Ins/Del genotype of CASP8 rs3834129 was related to a significantly decreased risk of stage I CWP (p=0.045; adjusted OR = 0.592; 95% CI 0.353-0.992), but not stage II or III CWP. Our study indicated that the heterozygous Ins/Del genotype of CASP8 rs3834129 significantly decreased CWP risk in a Chinese Han population.

An analysis of contributing mining factors in coal workers\u2019 pneumoconiosis prevalence in the United States coal mines, 1986\u20132018

In the United States, an unexpected and severe increase in coal miners’ lung diseases in the late 1990s prompted researchers to investigate the causes of the disease resurgence. This study aims to scrutinize the effects of various mining parameters, including coal rank, mine size, mine operation type, coal seam height, and geographical location on the prevalence of coal worker's pneumoconiosis (CWP) in surface and underground coal mines. A comprehensive dataset was created using the U.S. Mine Safety and Health Administration (MSHA) Employment and Accident/Injury databases. The information was merged based on the mine ID by utilizing SQL data management software. A total number of 123,589 mine-year observations were included in the statistical analysis. Generalized Estimating Equation (GEE) model was used to conduct a statistical analysis on a total of 29,707, and 32,643 mine-year observations for underground and surface coal mines, respectively. The results of the econometrics approach revealed that coal workers in underground coal mines are at a greater risk of CWP comparing to those of surface coal operations. Furthermore, underground coal mines in the Appalachia and Interior regions are at a higher risk of CWP prevalence than the Western region. Surface coal mines in the Appalachian coal region are more likely to CWP development than miners in the Western region. The analysis also indicated that coal workers working in smaller mines are more vulnerable to CWP than those in large mine sizes. Furthermore, coal workers in thin-seam underground mine operations are more likely to develop CWP.

Respiratory traits and coal workers’ pneumoconiosis: Mendelian randomisation and association analysis

ObjectivesSusceptibility loci of idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease were also significantly associated with the predisposition of coal worker’s pneumoconiosis (CWP) in recent studies. However, only a few...

Associations of VDR gene polymorphisms with risk of coal workers' pneumoconiosis in Chinese Han population.

Some studies showed that the polymorphisms of vitamin D receptor (VDR) gene were associated with pulmonary diseases. However, the relationship between the VDR variations and susceptibility to coal worker's pneumoconiosis (CWP) remains unclear. The study aimed to determine the associations between VDR polymorphisms and susceptibility to CWP in Chinese Han population. The study involved 340 CWP patients and 312 healthy controls. The VDR polymorphisms were determined by DNA sequencing, and serum 25(OH)2D levels were detected by Ultra High-Performance Liquid Chromatography-Tandem Mass Spectrometry. The results showed that the VDR gene ApaI T allele increased the risk of CWP (OR=1.486, 95% CI=1.125-1.963, P=0.006) and ApaI GT genotype as well as TT genotype increased the risk of CWP (GT vs. GG, OR=1.461, 95% CI=1.048-2.038, P=0.025; TT vs. GG, OR=2.673, 95% CI=1.017-7.025, P=0.039). Five haplotypes were identified and we found that the TGGT haplotype was associated with a lower risk of CWP (OR=0.755, 95% CI=0.603-0.946, P=0.014). Meanwhile, multifactor dimensionality reduction analysis showed that the interaction between ApaI and exposure was the strongest, followed by TaqI and then BsmI. The study also found that the serum 25(OH)2D mean levels of the case group were significantly lower than that of the control group, and the serum 25(OH)2D mean levels of ApaI homozygous mutant and heterozygous mutant subjects were lower than that of the wild homozygosity, respectively (P<0.001). The results suggested that ApaI T allele and GT or TT genotype and lower 25(OH)2D levels were increased the risk of CWP in Chinese Han population.

NAF1 rs4691896 Is Significantly Associated with Coal Workers' Pneumoconiosis in a Chinese Han Population: A Case-Control Study.

BackgroundPrevious studies have demonstrated the important role of genetic predisposition in coal workers’ pneumoconiosis (CWP) in addition to environmental factors. The pathogenesis of pulmonary fibrosis disease is related to telomere activity. We performed this study to assess the association between genetic variants of telomere-related genes and the risk of CWP.Material/MethodsWe enrolled 652 CWP Chinese Han patients and 648 dust-exposed controls in this case-control design study, genotyping 8 single-nucleotide polymorphisms (SNPs) including TERT (rs2736100), TERC (rs10936599 and rs12696304), and NAF1 (rs7675998, rs3822304, rs12331717, rs936562 and rs4691896) using the Sequenom MassARRAY system.ResultsWe identified a significant allele association between NAF1 rs4691896 and CWP by comparing patients with controls (22.0% vs. 13.0%, odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.54–2.33, Pc=1.14×10−8). The genotype frequency of rs4691896 differed significantly between the patients and controls (Pc=1.49×10−8). In addition, rs4691896 was correlated with CWP in an additive genetic model (OR: 1.96, 95% CI: 1.58–2.44, Pc=8.96×10−9) and a dominant model (OR: 2.15, 95% CI: 1.70–2.73, Pc=2.39×10−9).ConclusionsOur study for the first time demonstrates an association between a telomere-related gene (NAF1) and CWP in a Chinese Han population, and provides valuable insight to further understand the possible pathogenetic mechanism of fibrosis in CWP.

Associations of HMGB1 gene polymorphisms with risk of coal workers’ pneumoconiosis susceptibility in Chinese Han population

Background: High-mobility group box 1 (HMGB1) protein plays an important pathogenic role in various diseases such as pulmonary fibrosis. However, the relationship between variation of HMGB1 gene and susceptibility to coal worker's pneumoconiosis (CWP) remains unclear. The objective of the study was to determine the association between HMGB1 polymorphisms and CWP in Chinese Han population.Methods: The genotypes of HMGB1 gene rs1045411, rs2249825, rs1412125 and rs1360485 in 340 CWP patients and 312 healthy controls were determined and serum HMGB1 levels were detected.Results: Our finding showed that the HMGB1 rs1360485 G allele increased the risk of CWP in comparison with A allele (P = 0.005). HMGB1 rs1360485 GG genotype as well as AG+GG genotype increased the risk of CWP in comparison with AA genotype (P = 0.010, P = 0.025, respectively). Four haplotypes were identified and we found that the GCTA haplotype was associated with resistance to CWP (P = 0.005), while GCTG haplotype was associated with risk to CWP (P<0.001). Meanwhile, multifactor dimensionality reduction (MDR) analysis showed that the interaction between rs1360485 and exposure had the strongest, followed by rs2249825 and rs1412125. This study also found that the serum HMGB1 levels of the case group were significantly higher than that of the control group, and the serum HMGB1 levels of homozygous subjects with rs1360485 mutant were higher than that of the heterozygous wild type, respectively (P<0.001). Meanwhile, the levels of HMGB1 with GCTA haplotype was lower than with GCTG haplotype (P<0.001)Conclusion: Our findings indicated that HMGB1 gene rs1360485 polymorphism was associated with the susceptibility to CWP in Chinese Han population.

Association between tumor necrosis factor-α -308 Gauss/A polymorphism and risk of silicosis and coal workers pneumoconiosis in Chinese population

Background: Many studies have attempted to clarify the association between TNF-a -308G/A polymorphism and pneumoconiosis, but there has been no definite consensus to date. To further assess the effects of TNF-a -308G/A polymorphism on the risk of pneumoconiosis, a meta-analysis was performed in Chinese population.Methods: We searched the related literature in PubMed and Chinese databases through June 2018. The strength of the associations was assessed used pooled odds ratios (ORs) and 95% confidence intervals (CIs).Results: Nine case–control studies including 730 silicosis cases, 457 coal workers pneumoconiosis cases and 2429 controls were identified according to the inclusion criteria. In the total analyses, a significantly elevated risk was found in allelic model (OR = 1.41, 95% CI = 1.16–1.71). In the subgroup analyses by geographic area and type of pneumoconiosis, significant results were found both in North China (A versus G, OR = 1.33, CI = 1.05–1.69) and South China (A versus G, OR = 1.56, CI = 1.14–2.15); significant results were also found in silicosis (A versus G, OR = 1.40, CI = 1.11–1.78) and coal worker pneumoconiosis (A versus G, OR = 1.42, CI = 1.03–1.96).Conclusion: This meta-analysis suggested that TNF-a gene -308 G/A polymorphism is associated with increased silicosis and coal workers pneumoconiosis risk in the Chinese population, and further studies in other ethnic groups are required for definite conclusions.

Association Analysis Identifies New Risk Loci for Coal Workers' Pneumoconiosis in Han Chinese Men.

Coal worker's pneumoconiosis (CWP) is a debilitating and progressive occupational lung disease resulted from long-term inhalation of airborne silica-containing coal mine dust. Both environmental factors and genetic variations contribute to CWP. Our previous genome-wide association study (GWAS) revealed a tiny fraction of variants with the top associations in Chinese Han population. To identify novel susceptibility loci of CWP, functional variants with suboptimal associations in the GWAS scan were further studied here. Imputation was firstly performed to access the associations between ungenotyped variants and CWP risk, and suboptimal associations with p < 1.0 × 10-3 were annotated with genotype-tissue expression (GTEx) and dbNSFP. Further, expression quantitative trait loci (eQTL) and nonsynonymous variants were validated within an independent cohort with 703 CWP cases and 705 exposed controls. Comprehensively functional annotations were performed for identified single nucleotide polymorphism (SNPs) based on multiple bioinformatics databases and websites. We found 4 CWP risk-associated eQTL SNPs, including rs10797062 at 1q23.2 (p = 6.91 × 10-4, OR = 1.28), rs1667614 at 2q13.1 (p = 1.48 × 10-4, OR = 0.53), rs2540438 at 2q33.1 (p = 2.13 × 10-3, OR = 1.33), and rs2274554 at 13q31.1 (p = 9.01 × 10-5, OR = 1.35). Based on the results from GTEx, the identified variants were significantly associated with host genes in lung tissues: rs10797062-ATP1A4 (p = 8.60 × 10-11), rs1667614-FNBP1P1 (p = 1.00 × 10-20), rs2540438-ALS2CR12 (p = 1.90 × 10-7), and rs2274554-RBM26 (p = 5.00 × 10-6). Joint effect analysis showed the risk of CWP was significantly increased with the number of risk variant alleles in an allele-dosage manner (ptrend = 2.20 × 10-12). Enrichment pathway analysis suggested coexpressed genes of ATP1A4, FNBP1P1, and RBM26 were enriched in Ubiquitin mediated proteolysis pathway simultaneously. These results may provide a deeper understanding of the genetic predisposition of CWP.

LRBA Gene Polymorphisms and Risk of Coal Workers' Pneumoconiosis: A Case-Control Study from China.

The lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) is a member of the WDL-BEACH-WD (WBW) gene family. Defects in this gene are associated with the disordered autoimmunity in various diseases, including pulmonary fibrosis. In this study, we investigated the association between the functional polymorphisms in LRBA and risk of coal workers’ pneumoconiosis (CWP) in a Chinese population. Three potentially functional polymorphisms (rs2290846, rs3749574, and rs1782360) in LRBA were genotyped and analyzed in a case–control study, including 703 CWP cases and 705 controls. Genotyping was performed by the ABI 7900HT Real Time PCR system. Our results suggested that genotype rs2290846 AA was significantly associated with decreased risk of CWP (Adjusted OR = 0.61, 95% CI = 0.41–0.92), and the recessive model also supported the protective role of the genotype (Adjusted OR = 0.60, 95% CI = 0.40–0.89). Further, the polymorphism of rs2290846 decreased the CWP risk among cases over 27 years of dust exposure (adjusted OR = 0.51, 95% CI = 0.28–0.94) and non-smokers (adjusted OR = 0.58, 95% CI = 0.34–1.00). A potential role of rs2290846 AA has been proposed by expression quantitative trait loci (eQTL) and The Cancer Genome Atlas (TCGA). The present results suggest that LRBA SNPs are associated with CWP susceptibility in a Chinese population. Further studies focused on detailed mechanism or larger cohorts are warranted to validate our findings.

Polymorphisms in Long Noncoding RNA H19 Contribute to the Protective Effects of Coal Workers' Pneumoconiosis in a Chinese Population.

The H19 is a kind of long noncoding RNA, which has been implicated in multiple biological functions. However, the associations between genetic variants in H19 and susceptibility of coal workers’ pneumoconiosis (CWP) have been seldom reported. In the present study, three potential polymorphisms (rs2067051, rs217727, and rs2839702) in H19 were genotyped in a case-control study including 703 CWP cases and 705 controls. We found that individuals with the H19 rs2067051 CT/TT genotypes showed a decreased risk of CWP compared with those with the CC genotype (adjusted OR = 0.64, 95%CI = 0.49–0.83, p = 0.001). Further stratified analyses revealed that the associations between variant genotypes of rs2067051 and the risk of CWP were more prominent in subjects of non-smokers (adjusted OR = 0.55, 95%CI = 0.39–0.79, p = 0.001) and CWP patients with Stage I (adjusted OR = 0.63, 95%CI = 0.46–0.86, p = 0.004). Additionally, the protective effects of H19 rs2067051 were also evident in coal miners both with dust exposure years <25 years (adjusted OR = 0.63, 95%CI = 0.42–0.95, p = 0.026) and ≥25 years (adjusted OR = 0.57, 95%CI = 0.40–0.80, p = 0.001). Our results indicated that rs2067051 in the H19 gene is correlated with a deceased risk of CWP in a Chinese population, which may be a potential genetic marker for prevention and intervention of CWP. Further functional studies are warranted to validate our findings.

Plasma LncRNA-ATB, a Potential Biomarker for Diagnosis of Patients with Coal Workers' Pneumoconiosis: A Case-Control Study.

LncRNA-ATB (lncRNA was activated by transforming growth factor-β) has been reported to be involved in specific physiological and pathological processes in human diseases, and could serve as biomarkers for cancers. However, the role of lncRNA-ATB in coal workers’ pneumoconiosis (CWP) is still unknown. This study aimed to investigate the association between lncRNA-ATB and CWP. Quantitative real-time polymerase chain reaction was performed to detect plasma lncRNA-ATB expression in 137 CWP patients, 72 healthy coal miners and 168 healthy controls. LncRNA-ATB was significantly upregulated in CWP (p < 0.05). Compared with the healthy controls and healthy coal miners, the odds ratios (ORs) (95% confidence interval (CI)) for CWP were 2.57 (1.52–4.33) and 2.17 (1.04–4.53), respectively. LncRNA-ATB was positively associated with transforming growth factor-β1 (TGF-β1) (r = 0.30, p = 0.003) and negative correlated with vital capacity (VC) (r = −0.18, p = 0.033) and forced vital capacity (FVC) (r = −0.18, p = 0.046) in CWP patients. Compared with healthy controls, the area under the curve (AUC) was 0.84, resulting in a 71.17% sensitivity and 88.14% specificity. When compared with healthy coal miners, the AUC was 0.83, the sensitivity and specificity were 70.07% and 86.36%, respectively. LncRNA-ATB expression is commonly increased in CWP and significantly correlates with the TGF-β1 in CWP patients. Furthermore, elevated lncRNA-ATB was associated with CWP risk and may serve as a potential biomarker for CWP.

Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers’ Pneumoconiosis in Chinese Han Population

Coal workers’ pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52–0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41–1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series.

Associations of MMP-7 and OPN gene polymorphisms with risk of coal workers’ pneumoconiosis in a Chinese population: a case-control study

Background: The matrix metalloproteinase-7 (MMP-7) and osteopontin (OPN) are both multifunctional proteins with roles in inflammation, cell proliferation, tissue remodeling and so on, implicated in the pathogenesis of numerous conditions including pulmonary fibrosis. In this study, we investigated the associations between the potential functional polymorphisms in MMP-7 and OPN and the risk of coal workers’ pneumoconiosis (CWP) in a Chinese population.Methods: Four polymorphisms (rs10502001 in MMP-7, rs1126772, rs11728697 and rs9138 in OPN) were genotyped and analyzed in a case-control study of 697 CWP and 694 control subjects.Results: Our results revealed that three single nucleotide polymorphisms (SNPs, MMP-7 rs10502001, OPN rs1126772 and OPN rs11728697) were associated with increased risk of CWP under a recessive model (adjusted odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.01–3.20, p = 0.045 for MMP-7 rs10502001; adjusted OR = 2.09, 95% CI = 1.17–3.72, p = 0.013 for OPN rs1126772; adjusted OR = 2.48, 95% CI = 1.37–4.51, p = 0.003 for OPN rs11728697). Additionally, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (Ptrend = 0.003). Furthermore, logistic regression analysis revealed no significant interaction between SNPs and smoking status on CWP risk.Conclusions: Our results indicate that three functional SNPs (MMP-7 rs10502001, OPN rs11728697 and OPN rs1126772) are associated with an increased risk of CWP in a Chinese population.

Gene variance in microsomal epoxide hydrolase and the susceptibility of coal workers' pneumoconiosis

To explore whether the tagging single nucleotide polymorphisms (SNPs) within EPHX1 gene were involved in the genetic susceptibility to coal worker's pneumoconiosis (CWP) by case-control study. This study consisted of 697 CWP patients and 694 controls. All the subjects were Han Chinese, underground coal miners and recruited from coal mines of Xuzhou Mining Business Group Co Ltd.. The venous blood samples were obtained from all subjects and extracted genome DNA from the isolated leucocytes. Three SNPs were selected from the HapMap and the genotyping was done by the TaqMan method with the ABI 7900HT Real Time PCR system. The Single SNP analyses showed that the genotype frequencies of EPHX1 (rs2234922) was significantly associated with decreased risk of CWP under co-dominant model (OR = 0.22, 95% CI = 0.06~0.79, P = 0.020), recessive model (OR = 0.23, 95% CI = 0.06~0.82, P = 0.023), and addictive model (OR = 0.75, 95% CI = 0.58~0.96, P = 0.022). The further stratification analysis showed that the risk of CWP will significantly decreased in non-smoking groups (OR = 0.10, 95% CI = 0.01~0.83, P = 0.033). Our results suggest that individuals with the EPHX1 (rs223492) GG genotype was associated with a dereased risk of CWP, and it has a protective effect on the developing CWP.

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

BackgroundGlucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein (GITR) mainly affects the functions of effector T cells and regulatory T cells thus it may influence various diseases. Coal workers’ pneumoconiosis (CWP) is a serious occupational disease worldwide. In the present study, we examined the association between the functional polymorphisms in GITR and risk of CWP in a Chinese population. MethodsAn association study analyzing three polymorphisms (rs3753348, rs2298213, and rs11466668) in GITR were performed in a case–control study including 693 patients with CWP and 690 controls. Genotyping was carried out by Taqman method. ResultsThe GITR rs3753348 GG/GC genotypes significantly enhanced the risk of CWP (adjusted OR=1.32, 95%CI=1.02–1.71), compared with the CC genotype, particularly among subgroups of long exposure years (adjusted OR=1.47, 95%CI=1.06–2.04) and non-smokers (adjusted OR=1.45, 95%CI=1.01–2.09). Moreover, the polymorphism was significantly associated with risk for CWP cases with stage II. ConclusionsThis is the first report revealing an association between the GITR rs3753348 polymorphism and CWP, and our results suggest that the GITR rs3753348 polymorphism may be involved in the development and susceptibility of CWP.

Polymorphisms in SPARC and coal workers' pneumoconiosis risk in a Chinese population.

BackgroundThe SPARC is a crucial matricellular protein and may influence the course of various diseases like tumor metastasis and fibrosis. In the present study, we investigated the association between the potential functional polymorphisms in SPARC and coal workers' pneumoconiosis (CWP) risk in a Chinese population.MethodsFive potentially functional polymorphisms (rs1059279, rs1059829, rs1053411, rs2304052 and rs4958281) in SPARC were genotyped and analyzed in a case-control study including 697 CWP cases and 694 controls. The genotyping was used by the TaqMan method with the ABI 7900HT Real Time PCR system.ResultsOur results revealed that three SNPs (rs1059279, rs1059829, rs1053411) were significantly associated with increased risk of CWP under an additive model (OR = 1.35, 95%CI = 1.06–1.71, P = 0.015 for rs1059279; OR = 1.20, 95%CI = 1.03–1.39, P = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03–1.65, P = 0.025 for rs1053411). In the stratification analysis, significant associations were observed between each of these three SNPs and patients with 0–20 pack-years of smoking (OR = 1.73, 95%CI = 1.21–2.45 for rs1059279; OR = 1.48, 95%CI = 1.07–2.05 for rs105982; OR = 1.58, 95%CI = 1.13–2.22 for rs1053411). Furthermore, the association between rs1059279 and CWP risk remained significant among subjects with over 27 years of exposure (OR = 1.27, 95%CI = 1.03–1.56, P = 0.023). In the combined analysis of these five polymorphisms, individuals with multiple risk alleles had a higher risk of CWP (Ptrend = 0.015).ConclusionOur results indicate that three functional SPARC SNPs are associated with an increased risk of CWP in a Chinese population. Further functional research and validation studies with diverse populations are warranted to confirm our findings.

MUC5B promoter polymorphisms and risk of coal workers' pneumoconiosis in a Chinese population.

Coal workers' pneumoconiosis (CWP) is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Genetic variations have been recognized to be involved in the multi-factorial susceptibility to CWP, and MUC5B is a candidate lung fibrosis susceptibility gene. In the present study, we investigated possible genetic associations between three single nucleotide polymorphisms in MUC5B promoter region and CWP in a case-control study including 686 CWP patients and 680 controls. Genotyping was carried out by TaqMan method. Only rs2672794 allele and genotype frequencies distributions were significantly different between CWP patients and controls (P = 0.017 and 0.046 for allele and genotype, respectively). The MUC5B rs2672794 CC genotype was associated with a significantly increased risk of CWP, compared with the TT genotype. Moreover, individuals with TC/CC genotype had an obviously increased risk of CWP than those with TT genotype, particularly among subgroups of dust exposure <27 years and smokers. This is the first report showing an association between the MUC5B rs2672794 polymorphism and CWP, and our results suggest that MUC5B rs2672794 CC genotype could increase the risk of CWP. Further studies are warranted to confirm our findings.

Polymorphisms in cyclooxygenase-2 gene and risk of developing coal workers' pneumoconiosis: a case-control study.

Coal workers' pneumoconiosis (CWP) is characterized by progressive pulmonary fibrosis. Inflammation is crucial in the host response to silica and it contributes to pulmonary fibrosis. Cyclooxygenase-2 is involved in this process. The association between single-nucleotide polymorphisms in cyclooxygenase-2 gene with pneumoconiosis risk was investigated. An association study was conducted by analyzing two single-nucleotide polymorphisms of cyclooxygenase-2 (rs689466 and rs20417) in a case-control study involving 90 patients and 90 healthy individuals (controls). Genotyping was performed by the TaqMan method. The rs689466 AG and GG and rs689466 GC polymorphisms were significantly less frequent in patients than in controls. Cyclooxygenase-2 rs689466 and rs20417 variant genotypes exhibited 21% and 12% decreased CWP risk, respectively. Cyclooxygenase-2 rs689466 and rs20417 polymorphisms were associated with CWP risk.