Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA.
Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA.
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DOI：
10.1289/ehp.1206068
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发表时间：
2013-06
影响因子：
10.4
通讯作者：
Spanish Bladder Cancer/EPICURO Study Investigators
中科院分区：
文献类型：
--
作者：
Tajuddin SM;Amaral AF;Fernández AF;Rodríguez-Rodero S;Rodríguez RM;Moore LE;Tardón A;Carrato A;García-Closas M;Silverman DT;Jackson BP;García-Closas R;Cook AL;Cantor KP;Chanock S;Kogevinas M;Rothman N;Real FX;Fraga MF;Malats N;Spanish Bladder Cancer/EPICURO Study Investigators
背景：DNA甲基化改变与多种疾病有关。目的：我们评估了西班牙膀胱癌/EPICURO研究中892名对照受试者白细胞DNA长分布核素1(LINE-1)甲基化水平与遗传和非遗传特征之间的关系。方法：采用焦磷酸测序法测定LINE-1基因甲基化水平。个人数据包括人口统计学、吸烟状况、营养素摄入量、12种微量元素的趾甲浓度、异物代谢基因变异，以及一碳代谢途径中24个基因中的515个多态性。为了评估LINE-1甲基化水平(甲基化胞嘧啶的百分比)和潜在决定因素之间的关联，我们通过稳健的线性回归估计了β系数(βS)。结果：女性的Line-1甲基化水平低于男性(β=-0.7，p=0.0 2)。吸金色烟草的人比不吸烟的人甲基化程度低(β=-0.70，p=0.03)。趾甲砷浓度与Line-1甲基化呈负相关(β=-3.6p=0.003)。相比之下，铁(β=0.002，p=0.009)和镍(β=0.02，p=0.004)与Line-1甲基化呈正相关。DNMT3A(rs7581217-Per等位基因，β=0.3，p=0.002)、TCN2(rs9606756-GG，β=1.9，p=0.008；rs4820887-AA，β=4.0p=4.8×10-7；Rs9621049-TT，β=4.2p=4.7×10-9)、AS3MT(rs7085104-gG，β=0.7，p=0.001)、SLC19A1(rs914238，TC与TT：β=0.5，CC与TT：β=-0.3，全局p=0.0007)和MTHFS(rs1380642，CT与CC：β=0.3，TT与CC；β=-0.8，全局p=0.05)与LINE-1甲基化有关。结论：我们确定了在研究参与者中预测DNA甲基化的几个特征、环境因素和常见的遗传变异。
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.
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影响因子：
64.5
作者：
Bhutani N;Burns DM;Blau HM
通讯作者：
Blau HM
DOI：
10.1073/pnas.062066299
发表时间：
2002-04-16
影响因子：
11.1
作者：
Friso, S;Choi, SW;Selhub, J
通讯作者：
Selhub, J
影响因子：
3.7
作者：
Estecio, Marcos R. H.;Gharibyan, Vazganush;Shen, Lanlan;Ibrahim, Ashraf E. K.;Doshi, Ketan;He, Rong;Jelinek, Jaroslav;Yang, Allen S.;Yan, Pearlly S.;Huang, Tim H-M.;Tajara, Eloiza H.;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
6.8
作者：
Hopkins, WA;Staub, BP;Ford, NB
通讯作者：
Ford, NB