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影响化学介导的皮肤免疫毒性的遗传变异。

Genetic variants affecting chemical mediated skin immunotoxicity.

机构信息

Graduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba, Brazil.

Department of Genetics, Federal University of Paraná (UFPR), Curitiba, Brazil.

出版信息

J Toxicol Environ Health B Crit Rev. 2022 Feb 17;25(2):43-95. doi: 10.1080/10937404.2021.2013372. Epub 2022 Jan 3.

DOI:10.1080/10937404.2021.2013372
PMID:34979876
Abstract

The skin is an immune-competent organ and this function may be impaired by exposure to chemicals, which may ultimately result in immune-mediated dermal disorders. Interindividual variability to chemical-induced skin immune reactions is associated with intrinsic individual characteristics and their genomes. In the last 30-40 years, several genes influencing susceptibility to skin immune reactions were identified. The aim of this review is to provide information regarding common genetic variations affecting skin immunotoxicity. The polymorphisms selected for this review are related to xenobiotic-metabolizing enzymes ( and genes), antioxidant defense (, and genes), aryl hydrocarbon receptor signaling pathway ( and genes), skin barrier function transepidermal water loss (, and genes), inflammation (, and genes), major histocompatibility complex (MHC) and neuroendocrine system peptides ( genes). These genes present variants associated with skin immune responses and diseases, as well as variants associated with protecting skin immune homeostasis following chemical exposure. The molecular and association studies focusing on these genetic variants may elucidate their functional consequences and contribution in the susceptibility to skin immunotoxicity. Providing information on how genetic variations affect the skin immune system may reduce uncertainties in estimating chemical hazards/risks for human health in the future.

摘要

皮肤是一个具有免疫功能的器官,这种功能可能会因接触化学物质而受损,而这最终可能导致免疫介导的皮肤疾病。个体间对化学物质引起的皮肤免疫反应的差异与内在个体特征及其基因组有关。在过去的 30-40 年中,已经确定了几个影响皮肤免疫反应易感性的基因。本文的目的是提供有关影响皮肤免疫毒性的常见遗传变异的信息。本文选择的多态性与外源性代谢酶(和基因)、抗氧化防御(、和基因)、芳烃受体信号通路(和基因)、皮肤屏障功能经皮水分流失(、和基因)、炎症(、和基因)、主要组织相容性复合体(MHC)和神经内分泌系统肽(基因)有关。这些基因存在与皮肤免疫反应和疾病相关的变异,以及与化学暴露后保护皮肤免疫稳态相关的变异。针对这些遗传变异的分子和关联研究可能阐明其功能后果及其对皮肤免疫毒性易感性的贡献。提供有关遗传变异如何影响皮肤免疫系统的信息,可以减少未来评估化学危害/风险对人类健康的不确定性。

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