Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA

被引：63

作者：

Tajuddin, Salman M. ^{[1
]}

Amaral, Andre F. S. ^{[1
]}

Fernandez, Agustin F. ^{[2
]}

Rodriguez-Rodero, Sandra ^{[2
]}

Maria Rodriguez, Ramon ^{[2
]}

Moore, Lee E. ^{[3
]}

Tardon, Adonina ^{[4
]}

Carrato, Alfredo ^{[5
,6
]}

Garcia-Closas, Montserrat ^{[7
]}

Silverman, Debra T. ^{[3
]}

Jackson, Brian P. ^{[8
]}

Garcia-Closas, Reina ^{[9
]}

Cook, Ashley L. ^{[1
]}

Cantor, Kenneth P. ^{[10
]}

Chanock, Stephen ^{[3
]}

Kogevinas, Manolis ^{[11
]}

Rothman, Nathaniel ^{[3
]}

Real, Francisco X. ^{[12
,13
]}

Fraga, Mario F. ^{[2
,14
]}

Malats, Nuria ^{[1
]}

机构：

[1] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid 28029, Spain

[2] IUOPA, Canc Epigenet Lab, Oviedo, Spain

[3] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[4] Univ Oviedo, Oviedo, Spain

[5] Hosp Gen Univ Elche, Elche, Spain

[6] Hosp Ramon & Cajal, E-28034 Madrid, Spain

[7] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England

[8] Dartmouth Coll, Dept Earth Sci, Trace Element Anal Core, New Spring, MD USA

[9] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain

[10] KP Cantor Environm LLC, Silver Spring, MD USA

[11] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain

[12] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid 28029, Spain

[13] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain

[14] CSIC, CNB, Dept Immunol & Oncol, Madrid, Spain

来源：

ENVIRONMENTAL HEALTH PERSPECTIVES | 2013年 / 121卷 / 06期

基金：

美国国家卫生研究院;

关键词：

DNA methylation; epigenetics; LINE-1; one-carbon metabolism gene variants; smoking; trace elements; BLADDER-CANCER; EXPRESSION PROFILES; RISK; BLOOD; MUTATIONS; POLYMORPHISMS; ASSOCIATION; METABOLISM; GENOTYPE; TENDENCY;

D O I：

10.1289/ehp.1206068

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

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.

引用

页码：650 / 656

页数：7

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