<i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus

Aflatoxin B1 (AFB1), a well-established hepatic carcinogen, has limited research on early-stage epigenetic biomarkers for aflatoxin-induced liver damage. In this study, we investigated 168 unpackaged peanut oil (UPP) consumers to evaluate associations among AFB1 exposure, HBV infection, <i>RUN...

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Main Authors: Yunying Mo, Xiaodan Lu, Shixiong Zheng, Junfeng Deng, Shihan Huang, Ye Hong, Xiaoyu Xian, Aliya Yijiati, Xingyu Yu, Xunwu Luo, Miner Xiao, Xingfen Yang, Michael N. Routledge, Yunyun Gong, Zhini He
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Toxics
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Online Access:https://www.mdpi.com/2305-6304/13/6/425
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author Yunying Mo
Xiaodan Lu
Shixiong Zheng
Junfeng Deng
Shihan Huang
Ye Hong
Xiaoyu Xian
Aliya Yijiati
Xingyu Yu
Xunwu Luo
Miner Xiao
Xingfen Yang
Michael N. Routledge
Yunyun Gong
Zhini He
author_facet Yunying Mo
Xiaodan Lu
Shixiong Zheng
Junfeng Deng
Shihan Huang
Ye Hong
Xiaoyu Xian
Aliya Yijiati
Xingyu Yu
Xunwu Luo
Miner Xiao
Xingfen Yang
Michael N. Routledge
Yunyun Gong
Zhini He
author_sort Yunying Mo
collection DOAJ
description Aflatoxin B1 (AFB1), a well-established hepatic carcinogen, has limited research on early-stage epigenetic biomarkers for aflatoxin-induced liver damage. In this study, we investigated 168 unpackaged peanut oil (UPP) consumers to evaluate associations among AFB1 exposure, HBV infection, <i>RUNX3</i> methylation, and liver function. Our findings indicated an average daily AFB1 intake of 3.14 ng/kg·bw/day from UPP oil consumption. The high AFB1 exposure group exhibited significantly elevated gamma-glutamyl transferase (GGT) levels compared with the low AFB1 exposure group (<i>p</i> = 0.030). AFB1 exposure was negatively correlated with methylation status at the 2nd, 8th, and 9th CpG sites of <i>RUNX3</i> (r<sub>s</sub> = −0.196, −0.192, −0.181, <i>p</i> = 0.021, 0.024, 0.036). Furthermore, methylation at the 8th and 9th CpG sites positively correlated with GGT (r<sub>s</sub> = 0.206, 0.203, <i>p</i> = 0.019, 0.024). HBV infection significantly influenced <i>RUNX3</i> methylation, with the HBsAg<sup>+</sup> group exhibiting 16.25% lower methylation (<i>p</i> < 0.05). Stratified analysis by HBV and AFB1 revealed that in the low AFB1 exposure subgroup, <i>RUNX3</i> methylation in the HBsAg<sup>+</sup> group exhibited a significant 26.38% reduction compared with the HBsAg<sup>−</sup> group. These results indicated that AFB1 and HBV independently and synergistically promote site-specific <i>RUNX3</i> hypomethylation. Our results implicated <i>RUNX3</i> methylation as a critical mediator in HBV-AFB1 co-exposure hepatotoxicity, potentially serving as a novel epigenetic biomarker for early liver damage detection.
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spelling doaj-art-07c942bc20164fd7907cfd09b6cf5b6a2025-08-20T03:26:56ZengMDPI AGToxics2305-63042025-05-0113642510.3390/toxics13060425<i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B VirusYunying Mo0Xiaodan Lu1Shixiong Zheng2Junfeng Deng3Shihan Huang4Ye Hong5Xiaoyu Xian6Aliya Yijiati7Xingyu Yu8Xunwu Luo9Miner Xiao10Xingfen Yang11Michael N. Routledge12Yunyun Gong13Zhini He14Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaThe Sixth Affiliated Hospital of Jinan University, Dongguan 523000, ChinaThe Sixth Affiliated Hospital of Jinan University, Dongguan 523000, ChinaFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaLeicester Medical School, University of Leicester, Leicester LE1 7RH, UKSchool of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UKFood Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou 510515, ChinaAflatoxin B1 (AFB1), a well-established hepatic carcinogen, has limited research on early-stage epigenetic biomarkers for aflatoxin-induced liver damage. In this study, we investigated 168 unpackaged peanut oil (UPP) consumers to evaluate associations among AFB1 exposure, HBV infection, <i>RUNX3</i> methylation, and liver function. Our findings indicated an average daily AFB1 intake of 3.14 ng/kg·bw/day from UPP oil consumption. The high AFB1 exposure group exhibited significantly elevated gamma-glutamyl transferase (GGT) levels compared with the low AFB1 exposure group (<i>p</i> = 0.030). AFB1 exposure was negatively correlated with methylation status at the 2nd, 8th, and 9th CpG sites of <i>RUNX3</i> (r<sub>s</sub> = −0.196, −0.192, −0.181, <i>p</i> = 0.021, 0.024, 0.036). Furthermore, methylation at the 8th and 9th CpG sites positively correlated with GGT (r<sub>s</sub> = 0.206, 0.203, <i>p</i> = 0.019, 0.024). HBV infection significantly influenced <i>RUNX3</i> methylation, with the HBsAg<sup>+</sup> group exhibiting 16.25% lower methylation (<i>p</i> < 0.05). Stratified analysis by HBV and AFB1 revealed that in the low AFB1 exposure subgroup, <i>RUNX3</i> methylation in the HBsAg<sup>+</sup> group exhibited a significant 26.38% reduction compared with the HBsAg<sup>−</sup> group. These results indicated that AFB1 and HBV independently and synergistically promote site-specific <i>RUNX3</i> hypomethylation. Our results implicated <i>RUNX3</i> methylation as a critical mediator in HBV-AFB1 co-exposure hepatotoxicity, potentially serving as a novel epigenetic biomarker for early liver damage detection.https://www.mdpi.com/2305-6304/13/6/425AFB1HBVliver function<i>RUNX3</i>methylation
spellingShingle Yunying Mo
Xiaodan Lu
Shixiong Zheng
Junfeng Deng
Shihan Huang
Ye Hong
Xiaoyu Xian
Aliya Yijiati
Xingyu Yu
Xunwu Luo
Miner Xiao
Xingfen Yang
Michael N. Routledge
Yunyun Gong
Zhini He
<i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
Toxics
AFB1
HBV
liver function
<i>RUNX3</i>
methylation
title <i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
title_full <i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
title_fullStr <i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
title_full_unstemmed <i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
title_short <i>RUNX3</i> Methylation: An Epigenetic Biomarker for Early Liver Damage Induced by Co-Exposure to Aflatoxin B1 and Hepatitis B Virus
title_sort i runx3 i methylation an epigenetic biomarker for early liver damage induced by co exposure to aflatoxin b1 and hepatitis b virus
topic AFB1
HBV
liver function
<i>RUNX3</i>
methylation
url https://www.mdpi.com/2305-6304/13/6/425
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