Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA

Tajuddin, Salman Muhammad; Amaral, André F.S.; Fernández, Agustín F.; Rodriguez Rodero, Sandra; Rodríguez, Ramón María; Moore, Lee E.; Tardón, Adonina; Carrato, Alfredo; García Closas, Montserrat; Silverman, Debra T.; Jackson, Brian P.; García Closas, Reina; Cook, Ashley L.; Cantor, Kenneth P; Chanock, Stephen J.; Kogevinas, Manolis; Rothman, Nathaniel; Real, Francisco X.; Malats i Riera, Núria

Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA

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dc.contributor.author Tajuddin, Salman Muhammadca
dc.contributor.author Amaral, André F.S.ca
dc.contributor.author Fernández, Agustín F.ca
dc.contributor.author Rodriguez Rodero, Sandraca
dc.contributor.author Rodríguez, Ramón Maríaca
dc.contributor.author Moore, Lee E.ca
dc.contributor.author Tardón, Adoninaca
dc.contributor.author Carrato, Alfredoca
dc.contributor.author García Closas, Montserratca
dc.contributor.author Silverman, Debra T.ca
dc.contributor.author Jackson, Brian P.ca
dc.contributor.author García Closas, Reinaca
dc.contributor.author Cook, Ashley L.ca
dc.contributor.author Cantor, Kenneth Pca
dc.contributor.author Chanock, Stephen J.ca
dc.contributor.author Kogevinas, Manolisca
dc.contributor.author Rothman, Nathanielca
dc.contributor.author Real, Francisco X.ca
dc.contributor.author Malats i Riera, Núriaca
dc.date.accessioned 2015-04-09T08:14:50Z
dc.date.available 2015-04-09T08:14:50Z
dc.date.issued 2013ca
dc.description.abstract Background: Altered DNA methylation has been associated with various diseases. Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study. Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression. Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10–7; rs9621049-TT, β = 4.2, p = 4.7 × 10–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation. Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.en
dc.description.sponsorship This work was partially supported by the Association for International Cancer Research (AICR; grant 09-0780, and a doctoral scholarship awarded to S.M.T.); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, MINECO, Spain (grants 00/0745, PI051436, PI061614, PI09-02102, and G03/174); Red Temática de Investigación Cooperativa en Cáncer (grant RD06/0020-RTICC); the U.S. National Institutes of Health (grant RO1-CA089715); a postdoctoral fellowship awarded to A.F.S.A. from the Fundación Científica de la AECC; Fundació Marató TV3; and The Johns Hopkins University Vredenburg Scholarship awarded to A.L.C.en
dc.format.mimetype application/pdfca
dc.identifier.citation Tajuddin SM, Amaral AFS, Fernandez AF, Rodriguez-Rodero S, Rodriguez RM, Moore LE et al. Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect. 2013;121(6):387-92. DOI: 10.1289/ehp.1206068ca
dc.identifier.doi http://dx.doi.org/10.1289/ehp.1206068
dc.identifier.issn 0091-6765ca
dc.identifier.uri http://hdl.handle.net/10230/23372
dc.language.iso engca
dc.publisher National Institute of Environmental Health Sciences (NIEHS)ca
dc.relation.ispartof Environmental Health Perspectives. 2013;121(6):387-92
dc.rights Reproduced with permission from Environmental Health Perspectivesca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.keyword DNA methylationen
dc.subject.keyword Epigeneticsen
dc.subject.keyword LINE-1en
dc.subject.keyword One-carbon metabolism gene variantsen
dc.subject.keyword Smokingen
dc.subject.keyword Trace elementsen
dc.subject.other Genòmicaca
dc.subject.other Carcinògensca
dc.title Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNAen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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