From blood to lung tissue: effect of cigarette smoke on DNA methylation and lung function.
From blood to lung tissue: effect of cigarette smoke on DNA methylation and lung function.
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DOI：
10.1186/s12931-018-0904-y
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发表时间：
2018-11-03
影响因子：
5.8
通讯作者：
Marike Boezen H
中科院分区：
文献类型：
--
作者：
de Vries M;van der Plaat DA;Nedeljkovic I;Verkaik-Schakel RN;Kooistra W;Amin N;van Duijn CM;Brandsma CA;van Diemen CC;Vonk JM;Marike Boezen H
遗传因素和环境因素在慢性阻塞性肺疾病的发生发展中起一定作用。表观基因组，更具体地说，DNA甲基化，被认为是这些因素之间的重要联系。我们推测DNA甲基化是吸烟影响COPD发生的途径之一。在这项研究中，我们的目标是确定全血中与香烟烟雾暴露和肺功能水平相关的CpG位点，并验证肺组织中的这些CpG位点。用稳健的线性回归分析研究了658名吸烟5年的当前吸烟者的基因组范围内吸烟年限和DNA甲基化之间的关系。通过中介分析，我们随后选择了也与肺功能水平相关的CpG位点。通过焦磷酸测序和表达定量性状甲基化(EQTM)分析，验证了肺组织中重要的CpG位点，以研究DNA甲基化与基因表达之间的关系。15个CpG位点与背包年限显著相关，其中10个与肺功能水平相关。我们验证了肺组织中的5个CpG位点，发现了DNA甲基化和基因表达之间的几个关联。这项研究首次证实了一组CpG位点与吸烟和感兴趣组织：肺组织中全血中的肺功能水平有关。本文的在线版本(10.1186/s12931-0180904-y)包含向授权用户提供的补充材料。
Genetic and environmental factors play a role in the development of COPD. The epigenome, and more specifically DNA methylation, is recognized as important link between these factors. We postulate that DNA methylation is one of the routes by which cigarette smoke influences the development of COPD. In this study, we aim to identify CpG-sites that are associated with cigarette smoke exposure and lung function levels in whole blood and validate these CpG-sites in lung tissue. The association between pack years and DNA methylation was studied genome-wide in 658 current smokers with >5 pack years using robust linear regression analysis. Using mediation analysis, we subsequently selected the CpG-sites that were also associated with lung function levels. Significant CpG-sites were validated in lung tissue with pyrosequencing and expression quantitative trait methylation (eQTM) analysis was performed to investigate the association between DNA methylation and gene expression. 15 CpG-sites were significantly associated with pack years and 10 of these were additionally associated with lung function levels. We validated 5 CpG-sites in lung tissue and found several associations between DNA methylation and gene expression. This study is the first to validate a panel of CpG-sites that are associated with cigarette smoking and lung function levels in whole blood in the tissue of interest: lung tissue. The online version of this article (10.1186/s12931-018-0904-y) contains supplementary material, which is available to authorized users.
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影响因子：
9.6
作者：
Hoesein, Firdaus A. A. Mohamed;Zanen, Pieter;Lammers, Jan-Willem J.
通讯作者：
Lammers, Jan-Willem J.
影响因子：
3.5
作者：
Shenker, Natalie S.;Polidoro, Silvia;Flanagan, James M.
通讯作者：
Flanagan, James M.
长时间暴露于颗粒污染，与谷胱甘肽途径相关的基因以及一群老年人中的DNA甲基化。
影响因子：
10.4
作者：
Madrigano J;Baccarelli A;Mittleman MA;Wright RO;Sparrow D;Vokonas PS;Tarantini L;Schwartz J
通讯作者：
Schwartz J
影响因子：
30.8
作者：
Hobbs BD;de Jong K;Lamontagne M;Bossé Y;Shrine N;Artigas MS;Wain LV;Hall IP;Jackson VE;Wyss AB;London SJ;North KE;Franceschini N;Strachan DP;Beaty TH;Hokanson JE;Crapo JD;Castaldi PJ;Chase RP;Bartz TM;Heckbert SR;Psaty BM;Gharib SA;Zanen P;Lammers JW;Oudkerk M;Groen HJ;Locantore N;Tal-Singer R;Rennard SI;Vestbo J;Timens W;Paré PD;Latourelle JC;Dupuis J;O'Connor GT;Wilk JB;Kim WJ;Lee MK;Oh YM;Vonk JM;de Koning HJ;Leng S;Belinsky SA;Tesfaigzi Y;Manichaikul A;Wang XQ;Rich SS;Barr RG;Sparrow D;Litonjua AA;Bakke P;Gulsvik A;Lahousse L;Brusselle GG;Stricker BH;Uitterlinden AG;Ampleford EJ;Bleecker ER;Woodruff PG;Meyers DA;Qiao D;Lomas DA;Yim JJ;Kim DK;Hawrylkiewicz I;Sliwinski P;Hardin M;Fingerlin TE;Schwartz DA;Postma DS;MacNee W;Tobin MD;Silverman EK;Boezen HM;Cho MH;COPDGene Investigators;ECLIPSE Investigators;LifeLines Investigators;SPIROMICS Research Group;International COPD Genetics Network Investigators;UK BiLEVE Investigators;International COPD Genetics Consortium
通讯作者：
International COPD Genetics Consortium
影响因子：
3.7
作者：
Tsaprouni, Loukia G.;Yang, Tsun-Po;Deloukas, Panos
通讯作者：
Deloukas, Panos