Background

Chronic diseases have become main killers affecting the health of human, and environmental pollution is a major health risk factor that cannot be ignored. It has been reported that exogenous chemical residues including pesticides, herbicides, fungicides, veterinary drugs and persistent organic pollutants are associated with chronic diseases. However, the evidence for their relationship is equivocal and the underlying mechanisms are unclear.

Objectives

We aim to investigate the linkages between serum exogenous chemical residues and 5 main chronic diseases including obesity, hyperuricemia, hypertension, diabetes and dyslipidemia, and further reveal the metabolic perturbations of chronic diseases related to exogenous chemical residue exposure, then gain potential mechanism insight at the metabolic level.

Methods

LC-MS-based targeted and nontargeted methods were respectively performed to quantify exogenous chemical residues and acquire metabolic profiling of 496 serum samples from chronic disease patients. Non-parametric test, correlation and regression analyses were carried out to investigate the association between exogenous chemical residues and chronic diseases. Metabolome-wide association study combined with the meeting-in-the-middle strategy and mediation analysis was performed to reveal and explain exposure-related metabolic disturbances and their risk to chronic diseases.

Results

In the association analysis of 106 serum exogenous chemical residues and 5 chronic diseases, positive associations of serum perfluoroalkyl substances (PFASs) with hyperuricemia were discovered while other associations were not significant. 240 exposure markers of PFASs and 84 disease markers of hyperuricemia were found, and 47 of them were overlapped and considered as putative effective markers. Serum uric acid, amino acids, cholesterol, carnitines, fatty acids, glycerides, glycerophospholipids, ceramides, and a part of sphingolipids were positively correlated with PFASs and associated with increased risk for hyperuricemia. Creatine, creatinine, glyceryl monooleate, phosphatidylcholine 36:6, phosphatidylethanolamine 40:6, cholesterol and sphingolipid 36:1;2O were significant markers which mediated the associations of the residues with hyperuricemia.

Conclusions

Our study demonstrated a significantly positive association between PFASs exposure and hyperuricemia. The most significant metabolic abnormality was lipid metabolism which not only was positively associated with PFASs, but also increased the risk of hyperuricemia.

中文翻译：

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5种主要慢性病人群血清外源性化学残留的全代谢组关联研究

背景

慢性病已成为影响人类健康的主要杀手，环境污染是不可忽视的主要健康风险因素。据报道，包括农药、除草剂、杀菌剂、兽药和持久性有机污染物在内的外源性化学残留物与慢性疾病有关。然而，它们之间关系的证据是模棱两可的，潜在的机制尚不清楚。

目标

我们旨在研究血清外源性化学残留物与肥胖、高尿酸血症、高血压、糖尿病和血脂异常等 5 种主要慢性疾病之间的联系，进一步揭示与外源性化学残留物暴露相关的慢性疾病的代谢扰动，从而获得潜在的机制洞察。代谢水平。

方法

分别采用基于 LC-MS 的靶向和非靶向方法来量化外源性化学残留物并获取来自慢性病患者的 496 份血清样本的代谢谱。采用非参数检验、相关性和回归分析，探讨外源性化学残留物与慢性病的关系。进行了全代谢组关联研究，结合中间会议策略和中介分析，以揭示和解释与暴露相关的代谢紊乱及其对慢性病的风险。

结果

在对106种血清外源性化学残留物与5种慢性病的关联分析中，发现血清全氟烷基物质（PFASs）与高尿酸血症呈正相关，其他相关性不显着。共发现240个PFASs暴露标志物和84个高尿酸血症疾病标志物，其中47个重叠，被认为是推定的有效标志物。血清尿酸、氨基酸、胆固醇、肉碱、脂肪酸、甘油酯、甘油磷脂、神经酰胺和部分鞘脂与 PFAS 呈正相关，并与高尿酸血症风险增加相关。肌酸、肌酐、甘油单油酸酯、磷脂酰胆碱 36:6、磷脂酰乙醇胺 40:6、胆固醇和鞘脂 36:1；

结论

我们的研究表明，PFASs 暴露与高尿酸血症之间存在显着的正相关。最显着的代谢异常是脂质代谢，不仅与PFASs呈正相关，而且会增加高尿酸血症的风险。