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黄曲霉毒素 B1 和微囊藻毒素-LR 共同暴露与代谢基因多态性对肝脏损伤的交互作用:重点关注 SLCO1B1 和 GSTP1。

Interaction Effects of AFB1 and MC-LR Co-exposure with Polymorphism of Metabolic Genes on Liver Damage: focusing on SLCO1B1 and GSTP1.

机构信息

Department of Environmental Hygiene, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China.

Department of Tropical Epidemiology, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China.

出版信息

Sci Rep. 2017 Nov 23;7(1):16164. doi: 10.1038/s41598-017-16432-z.

Abstract

AFB1 and MC-LR are two major environmental risk factors for liver damage worldwide, especially in warm and humid areas, but there are individual differences in health response of the toxin-exposed populations. Therefore, we intended to identify the susceptible genes in transport and metabolic process of AFB1 and MC-LR and find their effects on liver damage. We selected eight related SNPs that may affect liver damage outcomes in AFB1 and MC-LR exposed persons, and enrolled 475 cases with liver damage and 475 controls of healthy people in rural areas of China. The eight SNPs were genotyped by PCR and restriction fragment length polymorphism. We found that SLCO1B1 (T521C) is a risk factor for liver damage among people exposed to high AFB1 levels alone or combined with MC-LR, and that GSTP1 (A1578G) could indicate the risk of liver damage among those exposed to high MC-LR levels alone or combined with high AFB1 levels. However, GSTP1 (A1578G) could reduce the risk of liver damage in populations exposed to low MC-LR levels alone or combined with high AFB1 levels. In conclusion, SLCO1B1 (T521C) and GSTP1 (A1578G) are susceptible genes for liver damage in humans exposed to AFB1 and/or MC-LR in rural areas of China.

摘要

AFB1 和 MC-LR 是全球范围内导致肝损伤的两个主要环境风险因素,尤其是在温暖潮湿的地区,但接触毒素的人群对健康的反应存在个体差异。因此,我们旨在确定 AFB1 和 MC-LR 转运和代谢过程中的易感基因,并研究它们对肝损伤的影响。我们选择了 8 个可能影响 AFB1 和 MC-LR 暴露人群肝损伤结果的相关 SNP,并招募了 475 例肝损伤患者和 475 例来自中国农村地区的健康对照者。通过 PCR 和限制性片段长度多态性分析了这 8 个 SNP。我们发现,SLCO1B1(T521C)是 AFB1 水平高或与 MC-LR 联合暴露人群肝损伤的危险因素,而 GSTP1(A1578G)可指示 AFB1 水平高或与 MC-LR 联合暴露人群肝损伤的风险。然而,GSTP1(A1578G)可降低 AFB1 水平低或与 MC-LR 联合暴露人群肝损伤的风险。综上所述,SLCO1B1(T521C)和 GSTP1(A1578G)是中国农村地区人群接触 AFB1 和/或 MC-LR 后发生肝损伤的易感基因。

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