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Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations
The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA methylation patterns and subsequently influence disease risk by altering the expression of key genes. Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and st...
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| Published in: | Biological trace element research 2019-06, Vol.189 (2), p.437-446 |
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| container_title | Biological trace element research |
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| creator | Zhang, Yanting Li, Yuanyuan Luo, Lanrong He, Qian Gao, Yanhui Feng, Hongqi Zhao, Lijun Wei, Wei Fu, Songbo Sun, Dianjun |
| description | The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA methylation patterns and subsequently influence disease risk by altering the expression of key genes. Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research. |
| doi_str_mv | 10.1007/s12011-018-1504-x |
| format | article |
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Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research.</description><identifier>ISSN: 0163-4984</identifier><identifier>EISSN: 1559-0720</identifier><identifier>DOI: 10.1007/s12011-018-1504-x</identifier><identifier>PMID: 30220071</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arsenic ; Arsenic - toxicity ; Arsenicals ; Atomic absorption analysis ; Atomic absorption spectrophotometry ; Biochemistry ; Biomedical and Life Sciences ; Biotechnology ; Biotransformation ; Bisulfite ; CDH1 gene ; Deoxyribonucleic acid ; Detection ; DNA ; DNA (Cytosine-5-)-Methyltransferase 1 - genetics ; DNA (Cytosine-5-)-Methyltransferases - genetics ; DNA methylation ; DNA Methylation - drug effects ; DNA Methylation - genetics ; DNA Methyltransferase 3B ; DNA sequencing ; Drinking water ; E-cadherin ; Environmental Exposure - adverse effects ; Environmental factors ; Female ; Gene expression ; Gene polymorphism ; Genotype ; Genotypes ; Genotyping ; Glutathione transferase ; Health risks ; Humans ; Life Sciences ; Male ; Markers ; Middle Aged ; Nucleotides ; Nutrition ; Oncology ; Pathogenesis ; Polymorphism ; Populations ; Pretreatment ; Promoter Regions, Genetic - drug effects ; Promoter Regions, Genetic - genetics ; Promoters ; Single-nucleotide polymorphism ; Speciation ; Spectral analysis ; Spectrophotometers ; Spectrophotometry ; Spectrophotometry, Atomic ; Stochasticity ; Urine ; Water Pollutants, Chemical ; Young Adult</subject><ispartof>Biological trace element research, 2019-06, Vol.189 (2), p.437-446</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Biological Trace Element Research is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-6bff1dc88c2846ec98531f5f1eb520cdf3ab0332e564f397cef825bec771643c3</citedby><cites>FETCH-LOGICAL-c372t-6bff1dc88c2846ec98531f5f1eb520cdf3ab0332e564f397cef825bec771643c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30220071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yanting</creatorcontrib><creatorcontrib>Li, Yuanyuan</creatorcontrib><creatorcontrib>Luo, Lanrong</creatorcontrib><creatorcontrib>He, Qian</creatorcontrib><creatorcontrib>Gao, Yanhui</creatorcontrib><creatorcontrib>Feng, Hongqi</creatorcontrib><creatorcontrib>Zhao, Lijun</creatorcontrib><creatorcontrib>Wei, Wei</creatorcontrib><creatorcontrib>Fu, Songbo</creatorcontrib><creatorcontrib>Sun, Dianjun</creatorcontrib><title>Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations</title><title>Biological trace element research</title><addtitle>Biol Trace Elem Res</addtitle><addtitle>Biol Trace Elem Res</addtitle><description>The exposure/biotransformation of inorganic arsenic (iAs) may perturb DNA methylation patterns and subsequently influence disease risk by altering the expression of key genes. Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Arsenic</subject><subject>Arsenic - toxicity</subject><subject>Arsenicals</subject><subject>Atomic absorption analysis</subject><subject>Atomic absorption spectrophotometry</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biotechnology</subject><subject>Biotransformation</subject><subject>Bisulfite</subject><subject>CDH1 gene</subject><subject>Deoxyribonucleic acid</subject><subject>Detection</subject><subject>DNA</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1 - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferases - genetics</subject><subject>DNA methylation</subject><subject>DNA Methylation - drug effects</subject><subject>DNA Methylation - genetics</subject><subject>DNA Methyltransferase 3B</subject><subject>DNA sequencing</subject><subject>Drinking water</subject><subject>E-cadherin</subject><subject>Environmental Exposure - adverse effects</subject><subject>Environmental factors</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene polymorphism</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Genotyping</subject><subject>Glutathione transferase</subject><subject>Health risks</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Markers</subject><subject>Middle Aged</subject><subject>Nucleotides</subject><subject>Nutrition</subject><subject>Oncology</subject><subject>Pathogenesis</subject><subject>Polymorphism</subject><subject>Populations</subject><subject>Pretreatment</subject><subject>Promoter Regions, Genetic - drug effects</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Promoters</subject><subject>Single-nucleotide polymorphism</subject><subject>Speciation</subject><subject>Spectral analysis</subject><subject>Spectrophotometers</subject><subject>Spectrophotometry</subject><subject>Spectrophotometry, Atomic</subject><subject>Stochasticity</subject><subject>Urine</subject><subject>Water Pollutants, Chemical</subject><subject>Young Adult</subject><issn>0163-4984</issn><issn>1559-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kMtOwzAQRS0EoqXwAWxQJNaGGTvOY1n1AUgFuoANGytx7ZKqjYudSO3f4yoFVqxmpDn3jnQIuUa4Q4D03iMDRAqYURQQ090J6aMQOYWUwSnpAyacxnkW98iF9ysATFnOz0mPA2OhAPvkY1qoxjofDY3RqqnqZTSuwup03VTFOnrWzed-XTSVrSNrovHLMJo7u7GNDpmqjobO67pSdLLbWq8X0dxu2w73l-TMFGuvr45zQN6nk7fRI529PjyNhjOqeMoampTG4EJlmWJZnGiVZ4KjEQZ1KRioheFFCZwzLZLY8DxV2mRMlFqlKSYxV3xAbrverbNfrfaNXNnW1eGlZAhxnECaiEBhRylnvXfayK2rNoXbSwR5sCk7mzLYlAebchcyN8fmttzoxW_iR18AWAf4cKqX2v29_r_1G0SJgE4</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Zhang, Yanting</creator><creator>Li, Yuanyuan</creator><creator>Luo, Lanrong</creator><creator>He, Qian</creator><creator>Gao, Yanhui</creator><creator>Feng, Hongqi</creator><creator>Zhao, Lijun</creator><creator>Wei, Wei</creator><creator>Fu, Songbo</creator><creator>Sun, Dianjun</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QH</scope><scope>7QP</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H97</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope></search><sort><creationdate>20190601</creationdate><title>Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations</title><author>Zhang, Yanting ; Li, Yuanyuan ; Luo, Lanrong ; He, Qian ; Gao, Yanhui ; Feng, Hongqi ; Zhao, Lijun ; Wei, Wei ; Fu, Songbo ; Sun, Dianjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-6bff1dc88c2846ec98531f5f1eb520cdf3ab0332e564f397cef825bec771643c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Arsenic</topic><topic>Arsenic - toxicity</topic><topic>Arsenicals</topic><topic>Atomic absorption analysis</topic><topic>Atomic absorption spectrophotometry</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biotechnology</topic><topic>Biotransformation</topic><topic>Bisulfite</topic><topic>CDH1 gene</topic><topic>Deoxyribonucleic acid</topic><topic>Detection</topic><topic>DNA</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1 - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferases - genetics</topic><topic>DNA methylation</topic><topic>DNA Methylation - drug effects</topic><topic>DNA Methylation - genetics</topic><topic>DNA Methyltransferase 3B</topic><topic>DNA sequencing</topic><topic>Drinking water</topic><topic>E-cadherin</topic><topic>Environmental Exposure - adverse effects</topic><topic>Environmental factors</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene polymorphism</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Genotyping</topic><topic>Glutathione transferase</topic><topic>Health risks</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Markers</topic><topic>Middle Aged</topic><topic>Nucleotides</topic><topic>Nutrition</topic><topic>Oncology</topic><topic>Pathogenesis</topic><topic>Polymorphism</topic><topic>Populations</topic><topic>Pretreatment</topic><topic>Promoter Regions, Genetic - 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Interindividual variation in patterns of DNA methylation can be explained by the influence of environmental, genetic, and stochastic factors. Here, we examined promoter DNA methylation levels with urinary arsenical concentrations and investigated the genetic and nongenetic determinants of DNA methylation in 105 samples collected from populations in Shanxi Province, China, with high levels of arsenic in drinking water. Arsenic concentrations in water were determined by atomic absorption spectrophotometry (AA-6800, Shimadzu Co., Kyoto, Japan). Urine samples were measured using an atomic absorption spectrophotometer with an arsenic speciation pretreatment system (ASA-2sp, Shimadzu Co. Kyoto, Japan) for detection. Gene-specific (CDH1, EREG, ERCC2, GSTP1, and MGMT) DNA methylation was quantified by targeted bisulfite sequencing. Single-nucleotide polymorphism (SNP) genotyping was performed using a custom-by-design 2 × 48-Plex SNPscan™ Kit. These results revealed CDH1 with promoter DNA methylation levels associated with iAs. After the exclusion of confounding factors, age was correlated with increased methylation of the CDH1 gene. The susceptibility of the CDH1 and GSTP1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs2424932) GA genotype, and the susceptibility of the CDH1 gene promoters to methylation was increased in individuals carrying the DNMT3B (SNP rs6087990) TC genotype. Although the above results must still be replicated in larger samples, the findings improve our understanding of the pathogenesis of arsenic and may highlight certain DNA methylation markers as attractive surrogate markers for prevention research.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30220071</pmid><doi>10.1007/s12011-018-1504-x</doi><tpages>10</tpages></addata></record> |
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| subjects | Adolescent Adult Aged Aged, 80 and over Arsenic Arsenic - toxicity Arsenicals Atomic absorption analysis Atomic absorption spectrophotometry Biochemistry Biomedical and Life Sciences Biotechnology Biotransformation Bisulfite CDH1 gene Deoxyribonucleic acid Detection DNA DNA (Cytosine-5-)-Methyltransferase 1 - genetics DNA (Cytosine-5-)-Methyltransferases - genetics DNA methylation DNA Methylation - drug effects DNA Methylation - genetics DNA Methyltransferase 3B DNA sequencing Drinking water E-cadherin Environmental Exposure - adverse effects Environmental factors Female Gene expression Gene polymorphism Genotype Genotypes Genotyping Glutathione transferase Health risks Humans Life Sciences Male Markers Middle Aged Nucleotides Nutrition Oncology Pathogenesis Polymorphism Populations Pretreatment Promoter Regions, Genetic - drug effects Promoter Regions, Genetic - genetics Promoters Single-nucleotide polymorphism Speciation Spectral analysis Spectrophotometers Spectrophotometry Spectrophotometry, Atomic Stochasticity Urine Water Pollutants, Chemical Young Adult |
| title | Factors Affecting Differential Methylation of DNA Promoters in Arsenic-Exposed Populations |
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