Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Environ Res. 2024 Dec 15;263(Pt 2):120131. doi: 10.1016/j.envres.2024.120131. Epub 2024 Oct 9.
Air pollution is a well-established risk factor for several adverse health outcomes, but the specific molecular mechanisms, particularly those involving metabolic processes, remain incompletely understood.
To evaluate associations between long-term air pollutant exposure and circulating plasma metabolites in two sub-cohorts of the population-based Rotterdam Study.
We analyzed data from 1455 participants of sub-cohort I (mean age 76.9 years, 58% female, 2002-2004) and 1061 participants from sub-cohort III (mean age 62.6 years, 56% female, 2012-2014). Mean annual exposure to fine particulate matter (PM), black carbon, nitrogen dioxide, and ozone (measured both annually and in warm seasons only) were estimated at residential addresses using land use regression models. Plasma metabolites were measured by Metabolon Inc., using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Cross-sectional associations between each air pollutant and 940 metabolites were determined using linear regression models. Benjamini-Hochberg false discovery rate (FDR) was utilized to control for multiple testing. Enrichment analysis was performed on statistically significant associated metabolites to identify significant metabolic pathways (p-value <0.05).
In sub-cohort I, PM, black carbon, nitrogen dioxide, annual ozone and ozone in warm season were statistically significantly associated with, respectively, 63, 30, 20, 31, and 41 metabolites (FDR <0.05) mostly belonging to lipid and amino acid sub-classes, and unannotated metabolites. Sphinganine, X - 16576 and 2-pyrrolidinone displayed statistically significant associations across all five air pollutants. In sub-cohort III, black carbon, nitrogen dioxide and ozone in warm seasons were associated with a single unannotated metabolite (X - 24970), and annual ozone with two unannotated metabolites (X - 24970 and X - 24306). Enriched pathways identified in sub-cohort I included pyrimidine metabolism and steroid hormone biosynthesis.
Our study revealed associations of long-term air pollutant exposure with several metabolites and enrichment of two pathways, which are known to be involved in the adrenal and reproductive system and cell metabolism.
空气污染是多种不良健康后果的既定危险因素，但具体的分子机制，特别是涉及代谢过程的机制，仍不完全清楚。
在基于人群的鹿特丹研究的两个亚队列中，评估长期空气污染物暴露与循环血浆代谢物之间的关联。
我们分析了子队列 I（平均年龄 76.9 岁，女性占 58%，2002-2004 年）和子队列 III（平均年龄 62.6 岁，女性占 56%，2012-2014 年）中 1455 名参与者和 1061 名参与者的数据。使用土地利用回归模型，在居住地址处估算每年细颗粒物（PM）、黑碳、二氧化氮和臭氧（全年和仅在温暖季节测量）的平均年暴露量。使用 Metabolon Inc.，通过超高效液相色谱-串联质谱法测量血浆代谢物。使用线性回归模型确定每种空气污染物与 940 种代谢物之间的横断面关联。采用 Benjamini-Hochberg 假发现率（FDR）来控制多重检验。对具有统计学意义的相关代谢物进行富集分析，以确定显著的代谢途径（p 值 <0.05）。
在子队列 I 中，PM、黑碳、二氧化氮、全年臭氧和温暖季节臭氧分别与 63、30、20、31 和 41 种代谢物（FDR <0.05）呈统计学显著相关，这些代谢物主要属于脂质和氨基酸亚类，以及未注释的代谢物。鞘氨醇、X-16576 和 2-吡咯烷酮在所有五种空气污染物中均显示出统计学显著的关联。在子队列 III 中，黑碳、二氧化氮和温暖季节臭氧与单个未注释代谢物（X-24970）相关，全年臭氧与两个未注释代谢物（X-24970 和 X-24306）相关。在子队列 I 中确定的富集途径包括嘧啶代谢和甾体激素生物合成。
我们的研究揭示了长期空气污染物暴露与几种代谢物的关联，以及两个途径的富集，这两个途径已知参与肾上腺和生殖系统以及细胞代谢。
