Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma.
Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma.
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DOI：
10.1371/journal.pone.0004488
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Ho, Shuk-mei
中科院分区：
文献类型：
--
作者：
Perera, Frederica;Tang, Wan-yee;Herbstman, Julie;Tang, Deliang;Levin, Linda;Miller, Rachel;Ho, Shuk-mei
在纽约市的一个1700名儿童的纵向队列中，哮喘的患病率（>25%）是美国最高的。这种高风险可能部分是由经胎盘暴露于交通相关的多环芳烃（PAH）引起的，但缺乏PAH-哮喘关系的生物标志物信息。我们在这里假设，与经胎盘PAH暴露和/或儿童哮喘风险相关的表观遗传标记可以在胎儿组织中识别。母亲完成了个人产前空气监测PAH暴露测定。应用甲基化敏感限制性内切酶指纹图谱分析20例儿童脐带白色血细胞（UCWBC）DNA。超过30个DNA序列被确定，其甲基化状态取决于母体PAH暴露水平。其中6个序列与已知的含有一个或多个5′-CpG岛（5′-CGI）的基因同源。其中，酰基辅酶A合成酶长链家族成员3（ACSL 3）在UCWBC中的5′-CGI甲基化程度与最初20个队列儿童中匹配的胎儿胎盘组织中的基因表达水平之间显示出最高的一致性。因此，选择ACSL 3在56名队列儿童的更大样本中进行进一步研究。发现ACSL 3 5′-CGI甲基化与母亲空气中PAH暴露量超过2.41 ng/m3（OR = 13.8; p<0.001;灵敏度= 75%;特异性= 82%）和父母报告5岁以前儿童哮喘症状（OR = 3.9; p<0.05）显著相关。 因此，如果得到验证，UCWBC DNA中的甲基化ACSL 3 5′CGI可能是经胎盘PAH暴露的替代终点和/或环境相关哮喘的潜在生物标志物。该探索性报告为发现与其他暴露评估和/或出生队列中疾病关系调查相关的表观遗传生物标志物提供了新的蓝图。这些结果支持了晚年疾病发展的早期起源的新兴理论。
In a longitudinal cohort of ∼700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5′-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5′-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5′CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development.
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
11.2
作者：
Aqeilan, RI;Donati, V;Croce, CM
通讯作者：
Croce, CM
影响因子：
24.3
作者：
Bouzigon, E.;Siroux, V.;Pin, I.
通讯作者：
Pin, I.
DOI：
10.1083/jcb.200409099
发表时间：
2005-06-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Khaled AR;Bulavin DV;Kittipatarin C;Li WQ;Alvarez M;Kim K;Young HA;Fornace AJ;Durum SK
通讯作者：
Durum SK
影响因子：
14.9
作者：
BIRKENBIHL, RP;SUBRAMANI, S
通讯作者：
SUBRAMANI, S