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首页> 外文会议>Annual conference of the International Society of Exposure Science >Single nucleotide polymorphisrn ?617 C/A in the Nrf2 gene promoter modifies gene expression-air pollution relationships in subjects with coronary artery disease
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Single nucleotide polymorphisrn ?617 C/A in the Nrf2 gene promoter modifies gene expression-air pollution relationships in subjects with coronary artery disease

机译：Nrf2基因启动子中的单核苷酸多态性？617 C / A改变冠心病患者的基因表达与空气污染的关系

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Background: We previously found positive associations between traffic-related air pollution exposures and gene expression in Nrf2-mediated antioxidant response genes and other genes. We hypothesize that genetic variation in NRF2 will alter relationships between pollutant exposure and expression of Nrf2-mediated genes. Aims: We aimed to determine if the -617C＞A SNP in the Nrf2 promoter, a polymorphism shown to decrease binding and promoter activity, modifies our prior pollutant-gene expression relations. Methods: We measured whole blood gene expression levels weekly (12 weeks) in 40 subjects with coronary heart disease living in retirement communities in the Los Angeles area. We measured outdoor air pollutants: size-fractionated PM (including quasi-ultrafine PM＜0.25μm), elemental and organic carbon (EC, OC), black carbon (BC), polycyclic aromatic hydrocarbons in PM (PAH), and gases (NOx, 03). We estimated primary and secondary OC (OCpri, SOC) from total OC. We genotyped the -617 position of NRF2 by sequencing. We used mixed effects regression models to test effect modification with pollutant~*genotype interaction terms. We tested informative genes from our prior analysis: NRF2, HMOX1, SOD2, NQO1, GCLC, GCLM, CAT, GSTP1, CYP1B1, IL1B and SELP. Results: We identified 8 carriers of the risk allele (8AC, OAA) and 32 non-carriers (CC). We found pollutant-genotype interactions for NRF2, SOD2, CYP1B1, NQO1, IL1B and SELP. In 617A carriers, NRF2 expression was lower in association with several pollutants. For SOD2, carriers had higher expression with exposure to traffic pollutants including: qUFP, PAH, EC, BC, OCpri, and NOx; as well as OC and SOC. Among carriers, we found increased IL1B and SELP, and decreased CYP1B1 with exposure. Conclusion: Overall, we found complex relationships with possible support for both a direct (CYP1B1) and an indirect role (SOD2, IL1B and SELP) of Nrf2 in mediating the gene expression changes associated with air pollution exposure.
机译：背景：我们之前发现交通相关的空气污染暴露与Nrf2介导的抗氧化反应基因和其他基因中的基因表达之间存在正相关。我们假设NRF2的遗传变异将改变污染物暴露与Nrf2介导的基因表达之间的关系。目的：我们旨在确定Nrf2启动子中的-617C＞ A SNP是否能改变我们先前的污染物-基因表达关系，Nrf2启动子中的多态性已显示出会降低结合和启动子活性。方法：我们每周（12周）测量居住在洛杉矶地区退休社区的40例冠心病患者的全血基因表达水平。我们测量了室外空气污染物：尺寸分级的PM（包括小于0.25μm的准超细PM），元素和有机碳（EC，OC），黑碳（BC），PM中的多环芳烃（PAH）和气体（NOx） ，03）。我们根据总OC估算了主要和次要OC（OCpri，SOC）。我们通过测序对NRF2的-617位置进行了基因分型。我们使用混合效应回归模型来测试污染物〜*基因型相互作用项对效应的修正。我们从先前的分析中测试了有用的基因：NRF2，HMOX1，SOD2，NQO1，GCLC，GCLM，CAT，GSTP1，CYP1B1，IL1B和SELP。结果：我们确定了风险等位基因的8个携带者（8AC，OAA）和32个非携带者（CC）。我们发现NRF2，SOD2，CYP1B1，NQO1，IL1B和SELP的污染物-基因型相互作用。在617A携带者中，NRF2的表达与几种污染物相关联而较低。对于SOD2，承运商在暴露于交通污染物中的表达更高，包括qUFP，PAH，EC，BC，OCpri和NOx。以及OC和SOC。在携带者中，我们发现IL1B和SELP升高，而CYP1B1降低。结论：总体而言，我们发现Nrf2在介导与空气污染暴露相关的基因表达变化中的直接作用（CYP1B1）和间接作用（SOD2，IL1B和SELP）均可能存在复杂的关系。

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