Inherited genetic effects on arsenic metabolism: A comparison of effects on arsenic species measured in urine and in blood.
Inherited genetic effects on arsenic metabolism: A comparison of effects on arsenic species measured in urine and in blood.
复制标题
遗传对砷代谢的影响：对尿液和血液中砷种类影响的比较。
DOI：
10.1097/ee9.0000000000000230
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发表时间：
2022-12
影响因子：
3.6
通讯作者：
Pierce, Brandon L.
中科院分区：
文献类型：
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作者：
Tamayo, Lizeth, I;Kumarasinghe, Yohhan;Tong, Lin;Balac, Olgica;Ahsan, Habibul;Gamble, Mary;Pierce, Brandon L.
无机砷（iAs）是一种致癌物质，长期暴露与不良健康后果有关，包括癌症和心血管疾病。消耗的iAs可以经历砷甲基转移酶（AS 3 MT）催化的两个甲基化反应，产生单甲基化和二甲基化形式的砷（MMA和DMA）。iAs的甲基化有助于促进尿中砷的排泄，DMA构成了排泄的大部分砷物质。过去的研究已经确定了与砷代谢效率（AME）相关的AS 3 MT（10q24.32）和FTCD（21q22.3）区域的遗传变异，以尿中存在的每种物质的比例（iAs%，MMA%和DMA%）测量，但尚未研究它们与血液中存在的砷物质的关联。我们使用三项嵌套在健康影响和纵向研究（HEALS）中的研究数据-营养对砷毒性的影响研究，叶酸和氧化应激研究，以及叶酸和肌酸试验-以检查先前确定的遗传变异与334人尿液和血液中砷物种的关联。我们证实，已知影响尿中砷物质组成（代谢的排泄副产物）的AS 3 MT和FTCD中的遗传变异对血液中的砷物质（一种直接与许多器官相互作用的组织类型，包括那些容易产生砷毒性的组织）具有相似的影响。我们观察到的这种一致性为以下假设提供了进一步的支持：迄今为止鉴定的AME SNP影响砷代谢和消除的效率，从而影响砷的内部剂量和递送至毒性易感器官和组织的剂量。
Inorganic arsenic (iAs) is a carcinogen, and chronic exposure is associated with adverse health outcomes, including cancer and cardiovascular disease. Consumed iAs can undergo two methylation reactions catalyzed by arsenic methyltransferase (AS3MT), producing monomethylated and dimethylated forms of arsenic (MMA and DMA). Methylation of iAs helps facilitate excretion of arsenic in urine, with DMA composing the majority of arsenic species excreted. Past studies have identified genetic variation in the AS3MT (10q24.32) and FTCD (21q22.3) regions associated with arsenic metabolism efficiency (AME), measured as the proportion of each species present in urine (iAs%, MMA%, and DMA%), but their association with arsenic species present in blood has not been examined. We use data from three studies nested within the Health Effects and Longitudinal Study (HEALS)—the Nutritional Influences on Arsenic Toxicity Study, the Folate and Oxidative Stress study, and the Folic Acid and Creatine Trial—to examine the association of previously identified genetic variants with arsenic species in both urine and blood of 334 individuals. We confirm that the genetic variants in AS3MT and FTCD known to effect arsenic species composition in urine (an excreted byproduct of metabolism) have similar effects on arsenic species in blood (a tissue type that directly interacts with many organs, including those prone to arsenic toxicity). This consistency we observe provides further support for the hypothesis the AME SNPs identified to date impact the efficiency of arsenic metabolism and elimination, thereby influencing internal dose of arsenic and the dose delivered to toxicity-prone organs and tissues.