toxics Article The Relationship between Metabolic Syndrome and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms Tzu-Hua Chen 1,2,3 , Wei-Shyang Kung 4 , Hung-Yu Sun 5 , Joh-Jong Huang 3 , Jia-Yi Lu 1 , Kuei-Hau Luo 6 and Hung-Yi Chuang 1,7,8, *   Citation: Chen, T.-H.; Kung, W.-S.; Sun, H.-Y.; Huang, J.-J.; Lu, J.-Y.; Luo, K.-H.; Chuang, H.-Y. The Relationship between Metabolic Syndrome and Plasma Metals Modified by EGFR and TNF-α Gene Polymorphisms. Toxics 2021, 9, 225. https://doi.org/10.3390/toxics9090225 Academic Editor: Soisungwan Satarug Received: 4 August 2021 Accepted: 13 September 2021 Published: 16 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Public Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; 980264@kmuh.org.tw (T.-H.C.); u105570008@kmu.edu.tw (J.-Y.L.) 2 Department of Family Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan 3 Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan; 1030578@kmuh.org.tw 4 Department of Pediatrics, Chien Shin Hospital, Kaohsiung 80143, Taiwan; u104862002@kmu.edu.tw 5 Department of Family Medicine, Changhua Christian Hospital, Changhua 50006, Taiwan; 144107@cch.org.tw 6 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; u107800007@kmu.edu.tw 7 Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan 8 Ph.D. Program in Environmental and Occupational Medicine, Research Center for Environmental Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan * Correspondence: ericch@kmu.edu.tw; Tel.: +886-7312-1101 Abstract: With the escalating global prevalence of metabolic syndrome (MetS), it is crucial to detect the high-risk population early and to prevent chronic diseases. Exposure to various metals has been indicated to promote MetS, but the findings were controversial, and the effect of genetic modification was not considered. Epidermal growth factor receptor (EGFR) was proposed to be involved in the pathway of metabolic disorders, and tumor necrotic factor-α (TNF-α) was regarded as an early inflammatory biomarker for MetS. This research aimed to analyze the impact of EGFR and TNF-α gene polymorphisms on the prevalence of MetS under environmental or occupational exposure to metals. We gathered data from 376 metal industrial workers and 639 non-metal workers, including physical parameters, biochemical data, and plasma concentrations of six metals. According to the genomic database of Taiwan Biobank, 23 single nucleotide polymorphisms (SNPs) on EGFR gene and 6 SNPs on TNF-α gene were incorporated in our research. We applied multivariable logistic regression to analyze the probability of MetS with various SNPs and metals. Our study revealed some susceptible and protective EGFR and TNF-α genotypes under excessive exposure to cobalt, zinc, selenium, and lead. Thus, we remind the high-risk population of taking measures to prevent MetS. Keywords: metabolic disorders; metabolic syndrome; epidermal growth factor receptor (EGFR); TNF-α; single nucleotide polymorphism (SNP); metals; inflammation; insulin resistance; Taiwan biobank 1. Introduction Metabolic syndrome (MetS), a prodromal stage of cardiovascular disease (CVD) and type 2 diabetes, has attracted wide public attention because it may contribute to all- cause mortality [1,2]. The global prevalence of MetS is estimated to be 25% and still escalating [3,4]. Therefore, it is imperative to identify the high-risk population and develop preventive strategies to reduce the health burden of chronic diseases. In addition to dietary habits, exercise, and genetic inheritance [5], some research studies have indicated the associations between metal exposure and MetS, but the find- ings were controversial [6,7]. A Korean population-based study suggested that elevated blood lead level was associated with a higher prevalence of MetS [8]; on the contrary, an inverse association was observed between blood lead and MetS in the residents of the Toxics 2021, 9, 225. https://doi.org/10.3390/toxics9090225 https://www.mdpi.com/journal/toxics