Genome-wide differential gene expression in children exposed to air pollution in the Czech Republic

Leeuwen, Danitsja M. van; Herwijnen, Marcel H. M. van; Pedersen, Marie; Knudsen, Lisbeth E.; Kirsch‐Volders, Micheline; Srám, Radim J.; Staal, Yvonne C.M.; Bajak, Edyta; Delft, J.H.M. van; Kleinjans, Jos

doi:10.1016/j.mrfmmm.2006.05.032

Cited by 44 publications

(27 citation statements)

References 22 publications

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“…Studies of genome-wide response in a group of children living in a mining district in the northwest of the Czech Republic found a number of differentially expressed genes in peripheral blood cells compared with children living in a less polluted rural area. Genes affected by air pollution included those from the nucleosome assembly category (van Leeuwen et al 2006). These data indicate that both DNA structure and gene expression patterns can be affected by air pollutants.…”

Section: Introductionmentioning

confidence: 77%

Chronic exposure to ambient particulate matter alters cardiac gene expression patterns and markers of oxidative stress in rats

Simkhovich

Kleinman

Mehrian‐Shai

et al. 2010

Air Qual Atmos Health

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Exposure to ambient particulate matter (PM) significantly increases cardiovascular morbidity and mortality in the general population. We hypothesized that some components of PM can affect the gene expression patterns in the hearts of rats exposed for 3 months to filtered air (FA), coarse (CP; 2.51.5 (for both up-and down-regulated genes), we found three genes in the CP and nine genes in the UFP groups with significantly changed expression, compared with FA. No significant changes in gene expression patterns were observed in the FP group. In the UFP group thioredoxin interacting protein (Txnip), a negative regulator of an antioxidant enzyme thioredoxin, and cytochrome P450 (Cyp2e1), an enzyme involved in the metabolism of foreign substances demonstrated significant up-regulation (fold ratios 1.79 and 1.57, respectively, with false discovery rate, FDR<0.05). In the CP group there was also a trend towards increased Txnip expression (fold ratio 1.43, FDR>0.05) and significant increase in the Cyp2e1 expression (fold ratio 1.79, FDR<0.05). Changes in the Txnip and Cyp2e1 expression showed statistically significant positive correlation to each other (p<0.0009) and were confirmed by real-time PCR. In addition Txnip and Cyp2e1 expression demonstrated statistically significant moderate correlation with the levels of MDA in the heart. Upregulation of both Cyp2e1 and Txnip are observed in hearts of patients with certain cardiac diseases. Therefore, chronic exposure to CP and UFP directly affects expression of disease-relevant genes in the myocardium.

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Section: Introductionmentioning

confidence: 77%

Chronic exposure to ambient particulate matter alters cardiac gene expression patterns and markers of oxidative stress in rats

Simkhovich

Kleinman

Mehrian‐Shai

et al. 2010

Air Qual Atmos Health

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“…This method, which is called Comparative Analysis of Shapley value (shortly, CASh), is applied to real gene expression data concerning the gene expression in children differentially exposed to air pollution. CASh has been used to analyze the gene expression published in [23] of 23 children from the polluted area of Teplice (TP) and 24 children from the rural control area of Prachatice (PR), in the Czech Republic. Clustering methods show that the list of genes provided by CASh is informative enough to discriminate between Teplice subjects and Pracatice subjects on the basis of their gene expression profiles.…”

Section: Microarray Games For Gene Expression Analysismentioning

confidence: 99%

An overview of recent applications of Game Theory to bioinformatics

Moretti

Vasilakos

2010

Information Sciences

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“…From these studies, eight genes have been identified as promising biomarkers for environmental carcinogenesis. They encompass genes of which the expression differed significantly between carcinogen-exposed and nonexposed individuals, in addition to genes that correlated significantly with an established biomarker of early biological effect (i.e., MN frequencies) (van Leeuwen et al 2006(van Leeuwen et al , 2007. The aim of the present study was to monitor the expression of this set of genes in humans inhabiting specific regions in Flanders and to associate these with blood and urinary measures of established biomarkers of exposure and early biological effect.…”

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confidence: 99%

“…Besides experimental in vitro studies that were directed toward obtaining gene expression profiles from model carcinogens in human blood mononuclear cells (van Leeuwen et al 2005), a concise human population of smoking-discordant monozygotic twin pairs has been investigated; genes were identified of which the expression significantly differed in smokers compared with their nonsmoking, genetically identical siblings (van Leeuwen et al 2007). Furthermore, in a study of children from the Czech Republic, numerous gene expressions appeared relatively increased among children inhabiting a severely polluted area (van Leeuwen et al 2006). From these studies, eight genes have been identified as promising biomarkers for environmental carcinogenesis.…”

mentioning

confidence: 99%

“…The aim of the present study was to monitor the expression of this set of genes in humans inhabiting specific regions in Flanders and to associate these with blood and urinary measures of established biomarkers of exposure and early biological effect. We measured the expression levels of these eight key genescytochrome P450 1B1 (CYP1B1), activating transcription factor 4 (ATF4), mitogenactivated protein kinase 14 (MAPK14), superoxide dismutase 2 (Mn) (SOD2), chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) (CXCL1), diacylglycerol O-acyltransferase homolog 2 (mouse) (DGAT2), tigger transposable element derived 3 (TIGD3), and PTEN-induced putative kinase-1 (PINK1) (van Leeuwen et al 2006(van Leeuwen et al , 2007 (Table 1 …”

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confidence: 99%

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Transcriptome analysis in peripheral blood of humans exposed to environmental carcinogens: a promising new biomarker in environmental health studies

Leeuwen¹,

Gottschalk²,

Schoeters³

et al. 2008

European Journal of Cancer Supplements

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BACKGROUND:Human carcinogenesis is known to be initiated and/or promoted by exposure to chemicals that occur in the environment. Molecular cancer epidemiology is used to identify human environmental cancer risks by applying a range of effect biomarkers, which tend to be nonspecific and do not generate insights into underlying modes of action. Toxicogenomic technologies may improve on this by providing the opportunity to identify molecular biomarkers consisting of altered gene expression profiles. OBJECTIVES:The aim of the present study was to monitor the expression of selected genes in a random sample of adults in Flanders selected from specific regions with (presumably) different environmental burdens. Furthermore, associations of gene expression with blood and urinary measures of biomarkers of exposure, early phenotypic effects, and tumor markers were investigated. RESULTS: Individual gene expression of cytochrome p450 1B1, activating transcription factor 4, mitogen-activated protein kinase 14, superoxide dismutase 2 (Mn), chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha), diacylglycerol O-acyltransferase homolog 2 (mouse), tigger transposable element derived 3, and PTEN-induced putative kinase1 were measured by means of quantitative polymerase chain reaction in peripheral blood cells of 398 individuals. After correction for the confounding effect of tobacco smoking, inhabitants of the Olen region showed the highest differences in gene expression levels compared with inhabitants from the Gent and fruit cultivation regions. Importantly, we observed multiple significant correlations of particular gene expressions with blood and urinary measures of various environmental carcinogens. CONCLUSIONS: Considering the observed significant differences between gene expression levels in inhabitants of various regions in Flanders and the associations of gene expression with blood or urinary measures of environmental carcinogens, we conclude that gene expression profiling appears promising as a tool for biological monitoring in relation to environmental exposures in humans. Materials and MethodsStudy population. The study population consisted of 398 subjects from eight different regions of residence in Flanders, Belgium (Table 2). Participants were recruited within several communities or sectors of communities in each of the eight regions of interest, based on random sampling. Inclusion criteria were age 50-65 years, living in the region > 5 years, and being able to complete questionnaires in Dutch. Prior to blood collection, informed consent was obtained from all individuals. Study protocols were approved by the Institutional Review Board/Ethical Committee of Antwerp University. Participants completed a questionnaire covering age, sex, and smoking habits, among other items, and they donated a blood and urine sample for measurement of the biomarkers. The questionnaire was based partly on a questionnaire used in the pilot phase of the FLEHS project (Staessen et al. 2001) and supplemented with spe...

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Genome-wide differential gene expression in children exposed to air pollution in the Czech Republic

Cited by 44 publications

References 22 publications

Chronic exposure to ambient particulate matter alters cardiac gene expression patterns and markers of oxidative stress in rats

Chronic exposure to ambient particulate matter alters cardiac gene expression patterns and markers of oxidative stress in rats

An overview of recent applications of Game Theory to bioinformatics

Transcriptome analysis in peripheral blood of humans exposed to environmental carcinogens: a promising new biomarker in environmental health studies

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