Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA
Por:
Tajuddin, S, Amaral, A, Fernandez, A, Rodriguez-Rodero, S, Rodriguez, R, Moore, L, Tardon, A, Carrato, A, Garcia-Closas, M, Silverman, D, Jackson, B, Garcia-Closas, R, Cook, A, Cantor, K, Chanock, S, Kogevinas, M, Rothman, N, Real, F, Fraga, M, Malats, N and Spanish Bladder Canc EPICURO Study
Publicada:
1 jun 2013
Resumen:
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 (beta s) by robust linear regression.
RESULTS: Women had lower levels of LINE-1 methylation than men (beta = -0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (beta = -0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (beta = -3.6, p = 0.003). By contrast, iron (beta = 0.002, p = 0.009) and nickel (beta = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, beta = 0.3, p = 0.002), TCN2 (rs9606756-GG, beta = 1.9, p = 0.008; rs4820887-AA, beta = 4.0, p = 4.8 x 10(-7); rs9621049-TT, beta = 4.2, p = 4.7 x 10(-9)), AS3MT (rs7085104-GG, beta = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: beta = 0.5 and CC vs. TT: beta = -0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: beta = 0.3 and TT vs. CC; beta = -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.
Filiaciones:
Tajuddin, S:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain
Amaral, A:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain
Fernandez, A:
IUOPA, Canc Epigenet Lab, Oviedo, Spain
Rodriguez-Rodero, S:
IUOPA, Canc Epigenet Lab, Oviedo, Spain
Rodriguez, R:
IUOPA, Canc Epigenet Lab, Oviedo, Spain
Moore, L:
NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
Tardon, A:
Univ Oviedo, Oviedo, Spain
:
Hosp Gen Univ Elche, Elche, Spain
Hosp Ramon & Cajal, E-28034 Madrid, Spain
Garcia-Closas, M:
Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England
Silverman, D:
NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
Jackson, B:
Dartmouth Coll, Dept Earth Sci, Trace Element Anal Core, New Spring, MD USA
Garcia-Closas, R:
Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain
Cook, A:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain
Cantor, K:
KP Cantor Environm LLC, Silver Spring, MD USA
Chanock, S:
NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
Kogevinas, M:
Ctr Res Environm Epidemiol CREAL, Barcelona, Spain
Rothman, N:
NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA
Real, F:
Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain
Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain
Fraga, M:
IUOPA, Canc Epigenet Lab, Oviedo, Spain
CSIC, CNB, Dept Immunol & Oncol, Madrid, Spain
Malats, N:
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain
Green Submitted, Green Published, gold
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