Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children.
Genetic and epigenetic variations in inducible nitric oxide synthase promoter, particulate pollution, and exhaled nitric oxide levels in children.
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DOI：
10.1016/j.jaci.2011.09.037
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发表时间：
2012-01
期刊：
影响因子：
--
通讯作者：
Gilliland FD
中科院分区：
文献类型：
--
作者：
Salam MT;Byun HM;Lurmann F;Breton CV;Wang X;Eckel SP;Gilliland FD
诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）是气道中一氧化氮合成的主要酶。因此，呼出的一氧化氮（FeNO）的测量提供了iNOS活性的体内评估。短期暴露于空气污染、单倍型和NOS 2启动子DNA甲基化与iNOS表达和/或FeNO独立相关。我们的目的是研究环境空气污染物，NOS 2启动子单倍型和NOS 2启动子甲基化对儿童FeNO水平的影响。我们选择了940名儿童健康研究的参与者，他们提供了口腔样本，并在同一天进行了FeNO测量。使用亚硫酸氢盐聚合酶链反应焦磷酸测序测定来测量DNA甲基化。7个单核苷酸多态性捕获的单倍型多样性的NOS 2启动子。根据中心监测点获得的空气污染数据，估算了FeNO测量前7天空气动力学直径≤2.5μm和≤10μm的颗粒物（PM2.5和PM10）、臭氧和二氧化氮的平均水平。我们发现PM2.5、NOS 2启动子单倍型和iNOS甲基化对FeNO的影响相互关联。升高的7天平均PM2.5暴露与较低的iNOS甲基化相关（P=.01）。NOS 2启动子单倍型与NOS 2启动子甲基化总体相关（P=6.2 × 10−8）。一个共同的启动子单倍型、iNOS甲基化水平和PM2.5暴露对FeNO的影响存在交互作用（Pinteraction=.00007）。NOS 2启动子变异和短期PM2.5暴露影响iNOS甲基化这是第一个研究表明，在空气污染介导的表型表达的遗传和表观遗传变异的贡献。
Inducible nitric oxide synthase (iNOS, encoded by NOS2) is the major enzyme for nitric oxide synthesis in airways. As such, measurement of exhaled nitric oxide (FeNO) provides an in vivo assessment of iNOS activity. Short-term exposure to air pollution, haplotypes and DNA methylation in NOS2 promoter have been associated independently with iNOS expression and/or FeNO. We aimed to examine the effects of ambient air pollutants, NOS2 promoter haplotypes and NOS2 promoter methylation on FeNO level in children. We selected 940 participants in the Children’s Health Study who provided buccal samples and had undergone FeNO measurement on the same day. DNA methylation was measured using a bisulfite-polymerase chain reaction Pyrosequencing assay. Seven single nucleotide polymorphisms captured the haplotype diversity in the NOS2 promoter. Average particulate matter with aerodynamic diameter ≤2.5μm and ≤10μm (PM2.5 and PM10), ozone and nitrogen dioxide levels 7 days before FeNO measurement were estimated based on air pollution data obtained at central monitoring sites. We found interrelated effects of PM2.5, NOS2 promoter haplotypes and iNOS methylation on FeNO. Elevated 7-day average PM2.5 exposure was associated with lower iNOS methylation (P=.01). NOS2 promoter haplotypes were globally associated with NOS2 promoter methylation (P=6.2 × 10−8). There was interaction among one common promoter haplotype, iNOS methylation level and PM2.5 exposure on FeNO (Pinteraction=.00007). Promoter variants in NOS2 and short term PM2.5 exposure affect iNOS methylation. This is one of the first studies showing contributions of genetic and epigenetic variations in air pollution mediated phenotype expression.
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影响因子：
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DOI：
10.1073/pnas.062066299
发表时间：
2002-04-16
影响因子：
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作者：
Friso, S;Choi, SW;Selhub, J
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发表时间：
2010-03
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
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作者：
Boyle JO;Gümüs ZH;Kacker A;Choksi VL;Bocker JM;Zhou XK;Yantiss RK;Hughes DB;Du B;Judson BL;Subbaramaiah K;Dannenberg AJ
通讯作者：
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影响因子：
10.4
作者：
Delfino, Ralph J;Staimer, Norbert;Gillen, Dan;Tjoa, Thomas;Sioutas, Constantinos;Fung, Kochy;George, Steven C;Kleinman, Michael T
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