Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study.,Environmental Health Perspectives

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Exposome-Wide Ranking to Uncover Environmental Chemicals Associated with Dyslipidemia: A Panel Study in Healthy Older Chinese Adults from the BAPE Study.
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2024-09-06 , DOI: 10.1289/ehp13864
Enmin Ding _{1,

2} , Fuchang Deng ₁ , Jianlong Fang ₁ , Juan Liu ₁ , Wenyan Yan ₃ , Qiao Yao ₁ , Ke Miao ₁ , Yu Wang ₁ , Peijie Sun ₁ , Chenfeng Li ₁ , Yuanyuan Liu ₁ , Haoran Dong ₁ , Li Dong ₁ , Xu Zhang ₁ , Yifu Lu ₁ , Xiao Lin ₁ , Changming Ding ₁ , Tiantian Li _{1,

3} , Yali Shi ₄ , Yaqi Cai ₄ , Xiaohui Liu _{5,

6} , Krystal J Godri Pollitt ₇ , John S Ji ₈ , Shilu Tong _{1,

3,

9,

10} , Song Tang _{1,

3} , Xiaoming Shi _{1,

3,

11}

Affiliation

China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health (NIEH), Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
National Protein Science Technology Center, Tsinghua University, Beijing, China.
School of Life Sciences, Tsinghua University, Beijing, China.
Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
Vanke School of Public Health, Tsinghua University, Beijing, China.
School of Public Health, Institute of Environment and Population Health, Anhui Medical University, Hefei, China.
School of Public Health and Social Work, Queensland University of Technology, Brisbane, Australia.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NIEH, China CDC, Beijing, China.

BACKGROUND Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency >50% and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.

更新日期：2024-09-06

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