1. The methylation of the AMER3 gene mediates the negative association between urinary polycyclic aromatic hydrocarbon metabolites and fasting plasma glucose in non-smokers: A new clue for the development of hypoglycemic agents
- Author
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Mengyi Wang, Wencan Dai, Dongming Wang, Ge Mu, Xiuquan Nie, Zi Ye, Bin Wang, Shijie Yang, Jixuan Ma, Weihong Chen, and Yanjun Guo
- Subjects
Blood Glucose ,medicine.medical_specialty ,Environmental Engineering ,endocrine system diseases ,Health, Toxicology and Mutagenesis ,Urinary system ,0211 other engineering and technologies ,Polycyclic aromatic hydrocarbon ,02 engineering and technology ,Negative association ,010501 environmental sciences ,01 natural sciences ,Methylation ,Internal medicine ,medicine ,Environmental Chemistry ,Humans ,Hypoglycemic Agents ,Polycyclic Aromatic Hydrocarbons ,Waste Management and Disposal ,Gene ,0105 earth and related environmental sciences ,chemistry.chemical_classification ,021110 strategic, defence & security studies ,Plasma glucose ,Chemistry ,Fasting ,Non-Smokers ,Pollution ,Endocrinology ,CpG site ,Hypoglycemic Effects ,Biomarkers - Abstract
Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause various health damages. However, some PAH derivatives are still used as agents, and some of them have hypoglycemic effects. Till now, few studies explored the relationship between urinary PAH metabolites and fasting plasma glucose (FPG). In this study, A total of 2682 non-smokers in the second follow-up of the Wuhan-Zhuhai cohort were included to explore the relationship between urinary PAH metabolites and FPG. FPG related epigenome-wide association study (EWAS) was conducted among 212 never smokers, and the mediation analysis was performed to find potential mediator cytosine-phosphoguanine (CpG) sites in the above relationship. The concentration of total urinary PAH metabolites was 3.60 (2.37, 5.85) μg/mmol Cr. The urinary PAH metabolites were negatively associated with FPG. Each 1-U increase in ln-transformed levels of 1-hydroxynaphthalene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, or 2- hydroxyphenanthrene was associated with 0.008-, 0.007-, 0.010-, or 0.010- unit decreased in ln-transformed levels of FPG, respectively (all p 0.05). We found 28 new CpG sites related to FPG (FDR0.05) through EWAS. Mediation analysis found that cg11350141 on AMER3 mediated 41.91% of the negative association of total urinary PAH metabolites with FPG. These results provide a new clue for the development of hypoglycemic agents.
- Published
- 2021