Dataset Information

Polymorphisms in inflammasome genes and risk of coal workers' pneumoconiosis in a Chinese population.

ABSTRACT:

Background

Coal workers' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which triggers caspase 1-mediated IL-1? and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.

Methods

We performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1?, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.

Results

The NLRP3 rs1539019 TT genotype was associated with a significantly increased risk of CWP (adjusted odds ratio (OR)?=?1.39, 95% confidence interval (CI)?=?1.07-1.81), compared with the GG/GT genotype, in particular among smokers (adjusted OR?=?1.67, 95%CI?=?1.15-2.42). In addition, the polymorphism was significantly associated with risk of CWP patients with stage I.

Conclusions

This is the first report showing an association between the NLRP3 rs1539019 polymorphism and CWP, and suggests that this polymorphism may confer increased risk for the development of the disease. Further studies are warranted to confirm our findings.

SUBMITTER: Ji X

PROVIDER: S-EPMC3478280 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polymorphisms in inflammasome genes and risk of coal workers' pneumoconiosis in a Chinese population.

Ji Xiaoming X Hou Zhiguo Z Wang Ting T Jin Kexin K Fan Jingjing J Luo Chen C Chen Minjuan M Han Ruhui R Ni Chunhui C

PloS one 20121022 10

<h4>Background</h4>Coal workers' pneumoconiosis (CWP), resulting from the inhalation of silica-containing coal mine dust, is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Recently, it has been hypothesized that inflammasomes could have a crucial role in the host response to silica and recent studies show that the inflammasome contributes to inflammation and pulmonary fibrosis. NLRP3, CARD8 are components of the NLRP3 inflammasome, which t ...[more]

PMID: 23110140

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Project description:The interleukin 17A (IL-17A) which is located on chromosome 6p and has been linked to chronic inflammation, is an important candidate gene conferring coal workers' pneumoconiosis (CWP). The purpose of this study was to investigate the genetic association between single nucleotide polymorphisms (SNPs) of IL-17A and CWP in a Chinese population.We conducted a case-control study to investigate the role of four common SNPs in the IL-17A gene, and evaluated the relationship between these four SNPs and dust-exposure year, tobacco smoking and stages of CWP. A total of 1391 subjects was enrolled in this study, including 694 subjects in control group and 697 in case group. TaqMan based qRT-PCRs were taken to genotype rs2275913, rs3748067, rs4711998, and rs8193036 within the IL-17A gene. Luciferase assays were used to determine the effects of rs8193036 C?>?T alleles on the expression of IL-17A.Unconditional logistic regression analysis showed that the genotypes of rs3748067 AA (adjusted OR?=?0.43, 95 % CI?=?0.23-0.83) and rs8193036 TT (adjusted OR?=?0.59, 95 % CI?=?0.40-0.86) were associated with a decreased risk of CWP, particularly among subgroups of smokers (adjusted OR =0.34, 95 % CI?=?0.13-0.86 for rs3748076; adjusted OR?=?0.41, 95 % CI?=?0.23-0.71 for 8193036) and CWP cases with stage I (adjusted OR?=?0.45, 95 % CI?=?0.21-0.98 for rs3748076; adjusted OR?=?0.46, 95 % CI?=?0.28-0.74 for 8193036). Furthermore, the polymorphism of rs3748067 significantly reduced the CWP risk among cases with over 27 years of dust exposure (adjusted OR?=?0.42, 95 % CI?=?0.18-0.97). The luciferase assays in two cell lines showed that the rs8193036 C?>?T substitution could reduce the expression of IL-17A, which was consistent with the findings of our association study.The rs3748067 G?>?A and rs8193036 C?>?T polymorphisms decrease CWP risk. These findings could be helpful in identifying individuals at decreased risk for CWP and further studies are warranted to validate them.

Dataset Information

Polymorphisms in inflammasome genes and risk of coal workers' pneumoconiosis in a Chinese population.

Background

Methods

Results

Conclusions

Publications

Polymorphisms in inflammasome genes and risk of coal workers' pneumoconiosis in a Chinese population.

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