A Six-Nucleotide Insertion-Deletion Polymorphism in the<i>CASP8</i>Promoter is Associated with Risk of Coal Workers' Pneumoconiosis

Ni, Chunhui; Yang, Ye; Wang, Meilin; Qian, Haiyang; Song, Zhifang; Jia, Xiaomin; Zhou, Jianwei

doi:10.1080/15287390902841102

Cited by 14 publications

(11 citation statements)

References 16 publications

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“…No exon mutations have been discovered in TP63 suggesting that dysregulation may be caused by other regions of the gene such as the promoter regions. Sequence variants in promoters have been shown to be risk factors in numerous diseases including pneumoconiosis [17], auto-immune diseases [18], asthma [19], and β-thalassaemia [20]. A six-nucleotide promoter polymorphism has been described as a risk factor in multiple cancers such as lung, esophagus, stomach, colorectum, breast and cervix in Chinese populations [21].…”

Section: Resultsmentioning

confidence: 99%

Insertion/Deletion Polymorphisms in the ΔNp63 Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex

et al. 2012

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Bladder exstrophy epispadias complex (BEEC) is a severe congenital anomaly; however, the genetic and molecular mechanisms underlying the formation of BEEC remain unclear. TP63, a member of TP53 tumor suppressor gene family, is expressed in bladder urothelium and skin over the external genitalia during mammalian development. It plays a role in bladder development. We have previously shown that p63−/− mouse embryos developed a bladder exstrophy phenotype identical to human BEEC. We hypothesised that TP63 is involved in human BEEC pathogenesis. RNA was extracted from BEEC foreskin specimens and, as in mice, ΔNp63 was the predominant p63 isoform. ΔNp63 expression in the foreskin and bladder epithelium of BEEC patients was reduced. DNA was sequenced from 163 BEEC patients and 285 ethnicity-matched controls. No exon mutations were detected. Sequencing of the ΔNp63 promoter showed 7 single nucleotide polymorphisms and 4 insertion/deletion (indel) polymorphisms. Indel polymorphisms were associated with an increased risk of BEEC. Significantly the sites of indel polymorphisms differed between Caucasian and non-Caucasian populations. A 12-base-pair deletion was associated with an increased risk with only Caucasian patients (p = 0.0052 Odds Ratio (OR) = 18.33), whereas a 4-base-pair insertion was only associated with non-Caucasian patients (p = 0.0259 OR = 4.583). We found a consistent and statistically significant reduction in transcriptional efficiencies of the promoter sequences containing indel polymorphisms in luciferase assays. These findings suggest that indel polymorphisms of the ΔNp63 promoter lead to a reduction in p63 expression, which could lead to BEEC.

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Section: Resultsmentioning

confidence: 99%

Insertion/Deletion Polymorphisms in the ΔNp63 Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex

et al. 2012

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“…It acts as a crucial defensive barrier against malignant proliferation and tumorigenesis [7], [10], [27]. Previous studies have presented conflicting results regarding the potential role of genetic variants in the CASP8 gene promoter region in tumorigenesis [14], [15], [16], [17], [18], [20], [28], [29], [30]. In a pioneer study, genetic variant (rs3834129) in the CASP8 promoter region was associated with a wide range of solid cancers including lung, esophageal, gastric, colorectal, cervical, and breast cancers in Chinese populations by affecting the Sp1 transcriptional factor binding site and the CASP8 gene expression [14].…”

Section: Discussionmentioning

confidence: 99%

“…The indel polymorphism, rs3834129 (CTTACT/−, written as 6 bp/del in the following text), in the promoter region of the CASP8 gene was reported to be associated with susceptibility to a wide range of cancers including CRC in Chinese populations [14]. Although this variant was subsequently reported to be associated with the risk of coal workers and bladder cancers in Chinese populations [15], [16], the positive association was not replicated in subsequent large scale case-control studies in European and American populations [17], [18]. Genotypes TC and CC of another single nucleotide polymorphism (SNP), rs3769821 (T/C), which is also located in the promoter region of the CASP8 gene, was found to influence genetic susceptibility to non-Hodgkin’s lymphoma (NHL) in a pooled analysis of three populations from the United States of America and Australia [19].…”

Section: Introductionmentioning

confidence: 99%

Genetic Polymorphisms of the CASP8 Gene Promoter May Not Be Associated with Colorectal Cancer in Han Chinese from Southwest China

Xiao

Chang

et al. 2013

PLoS ONE

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PurposeCaspase 8 (CASP8) plays a critical role in the apoptotic pathway and aberrant regulation of this pathway causes many diseases including cancers. Genetic variants rs3834129 (CTTACT/−) and rs3769821 (T/C) in the promoter region of the CASP8 gene were documented to be associated with multiple solid cancers and non-Hodgkin’s lymphoma (NHL), respectively, despite of some controversies. We aimed to discern potential association of these two variants and rs113686495 (CTGTCATT/−), as well as CASP8 mRNA and protein expression levels with colorectal cancer (CRC) in Han Chinese.MethodsWe genotyped CASP8 genetic variants in 305 CRC patients and 342 healthy individuals from Kunming, Southwest China. Expression levels of CASP8 mRNA and protein were quantified in paired cancerous and paracancerous normal tissues by using real-time quantitative PCR and western blot, respectively. We compared the frequencies of alleles, genotypes, and haplotypes between the cases and controls. Correlation of CASP8 mRNA and protein expression levels in paired cancerous and paracancerous normal tissues from patients with different genotypes and clinical expression were also evaluated.ResultsThere was no association of the CASP8 genetic variants with CRC in our case-control study. The CASP8 gene mRNA expression levels in cancerous and paracancerous normal tissues were similar and there was no significant difference between subjects with different genotypes and clinical features. However, we found that CASP8 protein level was significantly lower in cancerous tissues than in paired paracancerous normal tissues.ConclusionsOur results suggest that the three CASP8 genetic variants may not be associated with CRC risk in Han Chinese from southwest China. Aberrant CASP8 protein expression may play a role in the pathogenesis of CRC.

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“…Genetic factors can modify the extent or severity of disease in susceptible individuals. Different genetic factors might be involved in the development of CWP [28], [29], [30], [31], and innate immune activation through NLRP3 inflammasomes sensing silica might be one of the immunologic mechanisms in CWP. Xu et al indicated that the activation of NLRP3 played a potential role in the development of pulmonary fibrosis [32].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

Hou

Wang

et al. 2012

PLoS ONE

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BackgroundCoal 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-1β and IL-18 release. In the present study, we investigated whether common single nucleotide polymorphisms (SNPs) in inflammasome genes are associated with CWP.MethodsWe performed an association study analyzing 3 NLRP3, 1 CARD8, 1 IL-1β, 2 IL-18 SNPs in a case-control study of 697 CWP and 694 controls. Genotyping was carried out by the TaqMan method.ResultsThe 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.ConclusionsThis 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.

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A Six-Nucleotide Insertion-Deletion Polymorphism in theCASP8Promoter is Associated with Risk of Coal Workers' Pneumoconiosis

Cited by 14 publications

References 16 publications

Insertion/Deletion Polymorphisms in the ΔNp63 Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex

Insertion/Deletion Polymorphisms in the ΔNp63 Promoter Are a Risk Factor for Bladder Exstrophy Epispadias Complex

Genetic Polymorphisms of the CASP8 Gene Promoter May Not Be Associated with Colorectal Cancer in Han Chinese from Southwest China

Polymorphisms in Inflammasome Genes and Risk of Coal Workers' Pneumoconiosis in a Chinese Population

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