一碳单位酶基因单核苷酸多态对砷代谢及中毒的影响

Effect of single nucleotide polymorphisms of one-carbon unit enzyme gene on arsenic metabolism and poisoning

砷是一种已知的毒物和人类致癌物,在自然界中广泛存在。慢性砷暴露可引起皮肤色素异常、过度角化及皮肤和内脏肿瘤为主的全身中毒,其机制到目前为止尚不十分清楚。砷化合物进入机体将发生甲基化代谢,砷甲基化代谢过程的甲基供体S-腺苷基甲硫氨酸(S-adenosyl methionine,SAM)来自以四氢叶酸为中心的一碳单位代谢环路,该环路受多种酶的调节,这些酶的单核苷酸多态性可能会由于影响SAM的供给而间接引起个体甲基化代谢的差异。本综述主要阐述一碳单位代谢环路中关键酶的功能、基因多态性及其与砷代谢和砷中毒发病风险之间的关联。

Arsenic,a known poison and human carcinogen,is widely found in nature.Chronic arsenic exposure can cause skin pigment abnormalities,hyperkeratosis and systemic poisoning dominated by skin and visceral tumors,and the mechanism is not well understood so far.The arsenic compound enters the body and undergoes methylation metabolism.The methyl donor S-adenosyl methionine(SAM)of arsenic methylation process is derived from a carbon unit centered on tetrahydrofolate,and the metabolic loop is regulated by a variety of enzymes.Single nucleotide polymorphisms of these enzymes may indirectly cause differences in methylation metabolism in individuals due to the effects of SAM supply.This review focuses on the functions of key enzymes in a single carbon metabolism loop,genetic polymorphisms and their association with arsenic metabolism and the risk of arsenic poisoning.