Heavy metal exposure and its effects on APOC3, CFAI, and ZA2G

Nam-Eun Kim; Min Heo; Hyeongyu Shin; Ah Ra Do; Jeeyoung Kim; Hee-Gyoo Kang; Sora Mun; Hyun Ju Yoo; Mi Jeong Kim; Jung-Woong Kim; Chul-Hong Kim; Young-Seoub Hong; Yong Min Cho; Heejin Jin; Kyungtaek Park; Woo Jin Kim; Sungho Won

doi:10.1016/j.jhazmat.2024.136574

Heavy metal exposure and its effects on APOC3, CFAI, and ZA2G

J Hazard Mater. 2024 Nov 20:482:136574. doi: 10.1016/j.jhazmat.2024.136574. Online ahead of print.

Authors

Nam-Eun Kim¹, Min Heo², Hyeongyu Shin², Ah Ra Do³, Jeeyoung Kim⁴, Hee-Gyoo Kang⁵, Sora Mun⁵, Hyun Ju Yoo⁶, Mi Jeong Kim⁶, Jung-Woong Kim⁷, Chul-Hong Kim⁸, Young-Seoub Hong⁹, Yong Min Cho¹⁰, Heejin Jin¹, Kyungtaek Park¹, Woo Jin Kim¹¹, Sungho Won¹²

Affiliations

¹ Institute of Health and Environment, Seoul National University, Seoul 08826, South Korea.
² Interdisciplinary Program in Bioinformatics, Seoul National University, 08826 Seoul, South Korea.
³ RexSoft Corp, Seoul 08826, South Korea.
⁴ Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
⁵ Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam 13135, South Korea.
⁶ Biomedical Research Center, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05535, South Korea.
⁷ Department of Life Science, College of Natural Sciences, Chung-Ang University, Seoul 06911, South Korea.
⁸ Department of Preventive Medicine, College of Medicine, Dong-A University, Busan 49315, South Korea.
⁹ Busan Environmental Health Center, Dong-A University, Busan 49315, South Korea; Environmental Health Center, Seokyeong University, Seoul 02713, South Korea.
¹⁰ Department of Nano Chemical and Biological Engineering, Seokyeong University, Seoul 02713, South Korea.
¹¹ Department of Internal Medicine and Environmental Health Center, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea. Electronic address: pulmo2@kangwon.ac.kr.
¹² Institute of Health and Environment, Seoul National University, Seoul 08826, South Korea; Interdisciplinary Program in Bioinformatics, Seoul National University, 08826 Seoul, South Korea; RexSoft Corp, Seoul 08826, South Korea; Department of Public Health Sciences, Seoul National University, Seoul 08826, South Korea. Electronic address: won1@snu.ac.kr.

PMID: 39579699
DOI: 10.1016/j.jhazmat.2024.136574

Abstract

Despite increasing heavy metal pollution, traditional epidemiology often fails to link exposure to health outcomes. This study used multi-omics to investigate associations between heavy metal exposure and health. Blood and urine samples from 294 participants in heavy metal-exposed and control areas were analyzed, revealing key biomarkers. Meta P analysis revealed consistent trends in apolipoprotein C3 (APOC3) expression, and mediation analysis showed significant effects of APOC3 and zinc-alpha-2-glycoprotein (ZA2G) on metabolites: the mediating effect of APOC3 from blood cadmium to serotonin was 0.023 (P < 0.001) and that to 3-phosphoglyceric acid (3PG) was 0.0125 (P = 0.002). Mendelian randomization confirmed the positive impact of APOC3 and Complement Factor I (CFAI) and the negative effect of ZA2G on metabolites, with apolipoprotein H (APOH) methylation significantly altering APOC3 (β = -0.22, P = 0.017), CFAI (β = 0.176, P = 0.035), and ZA2G (β = 0.139, P = 0.048) protein levels. Liver function variables, including albumin, total protein, calcium, and lactate dehydrogenase, correlated with 3PG and serotonin levels in the exposed areas. Sex-specific analysis showed that men exhibited stronger compensatory mechanisms via CFAI and myo-inositol, while women's greater vulnerability to heavy metal exposure highlighted the need for targeted interventions. These findings suggest APOH methylation affects APOC3, CFAI, and ZA2G levels, elevating 3PG, inosine monophosphate, and serotonin levels and harming liver function via lipolysis, supporting the use of these markers in health monitoring, therapies, and policies to limit heavy metal risks.

Keywords: APOC3; CFAI; Heavy metal; Liver function; Molecular biomarker; Multi-omics; ZA2G.