Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population.
Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population.
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不同的基因与颗粒物质和烟草烟雾相互作用，在影响一般人群的肺功能下降时与烟雾烟相互作用。
DOI：
10.1371/journal.pone.0040175
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Probst-Hensch NM
中科院分区：
文献类型：
--
作者：
Curjuric I;Imboden M;Nadif R;Kumar A;Schindler C;Haun M;Kronenberg F;Künzli N;Phuleria H;Postma DS;Russi EW;Rochat T;Demenais F;Probst-Hensch NM
氧化应激相关基因改变环境空气污染或吸烟对肺功能下降的影响。相互作用的影响可能是巨大的，但以前的研究大多集中在单个基因的主要影响。我们研究了这两种暴露与一系列氧化应激相关的候选基因和途径对肺功能下降的相互作用，并对比了暴露之间的相互作用。对于12679个单核苷酸多态性（SNPs），一秒用力呼气量（FEV 1）、FEV 1超过用力肺活量的变化（FEV 1/FVC），平均用力呼气流量在FVC的25 - 75%之间（FEF 25 -75）对间隔暴露于直径<10 µm的颗粒物（PM10）或吸烟包年（a），加性SNP效应（B），在669名具有GWAS数据的成年人中，（a）和（B）之间的交互作用项。通过自适应秩截乘积（ARTP）方法计算了152个基因和14个通路的相互作用p值，并在暴露之间进行了比较。对于名义上显著的基因的最强SNP，对比相互作用效应大小（p相互作用<0.05）。在3320名没有GWAS的SAPALDIA参与者中尝试复制MAF>10%的SNP。在SNP水平上，SNCA基因中的rs 2035268在11年内加速了FEV 1/FVC下降3.8%（pinteraction = 2.5×10−6），PARK 2基因中的rs 12190800在11年内减轻了FEV 1下降95.1 ml（pinteraction = 9.7×10−8），同时与PM10相互作用。 基因和途径名义上与PM10和packyears曝光相互作用有很大不同。CRISP 2基因与PM10在FEV 1/FVC下降方面存在显著的相互作用（pinteraction = 3.0×10−4）。 途径相互作用较弱。PARK 2和CRISP 2中最强SNP的复制没有成功。与对增加的氧化应激的分层反应一致，不同的基因和途径可能介导PM10和烟草烟雾对肺功能下降的影响。忽略环境暴露会错过这些模式，但实现足够的样本量和研究样本之间的可比性是具有挑战性的。
Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV1), FEV1 over forced vital capacity (FEV1/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF25-75) was regressed on interval exposure to particulate matter <10 µm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (pinteraction<0.05). Replication was attempted for SNPs with MAF>10% in 3320 SAPALDIA participants without GWAS. On the SNP-level, rs2035268 in gene SNCA accelerated FEV1/FVC decline by 3.8% (pinteraction = 2.5×10−6), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml pinteraction = 9.7×10−8) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (pinteraction = 3.0×10−4) on FEV1/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobacco smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challenging.
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DOI：
10.1007/s00038-005-4075-5
发表时间：
2005-01-01
期刊：
SOZIAL-UND PRAVENTIVMEDIZIN
影响因子：
--
作者：
Ackermann-Liebrich, U;Kuna-Dibbert, B;Leuenberger, P
通讯作者：
Leuenberger, P
影响因子：
10
作者：
Araujo JA;Nel AE
通讯作者：
Nel AE
影响因子：
5.6
作者：
Eisner, Mark D.;Wang, Yue;Tager, Ira B.
通讯作者：
Tager, Ira B.
影响因子：
158.5
作者：
Bouzigon, Emmanuelle;Corda, Eve;Demenais, Florence
通讯作者：
Demenais, Florence
影响因子：
10
作者：
Burney, P. G. J.;Hooper, R.
通讯作者：
Hooper, R.