Blood Gene Expression Profiling of an Early Acetaminophen Response (II). Homo sapiens

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. Overall design: Overdosed patients admitted to the emergency room. Five male and female individuals from 19 - 59 years old were admitted to the emergency room following an overdose on acetaminophen. The patients presented 12hrs to 4 days after ingestion. ALT and AST elevated peaking beyond 400 U/I and 120 U/I. Blood was collected 2 or 5 days following ingestion.

对乙酰氨基酚（acetaminophen）过量服用时可对肝脏造成不良影响。本研究以全血作为替代样本，筛选可作为对乙酰氨基酚诱导机体反应潜在早期预警指标的基因。在一项临床研究中，健康人类受试者每日服用4g对乙酰氨基酚或安慰剂片剂，持续7天，并在14天的研究周期内接受评估。对乙酰氨基酚应答者的丙氨酸氨基转移酶（ALT, Alanine aminotransferase）水平在给药后第4至9天出现升高，另有12个基因的表达谱在给药后24小时内发生显著改变。这些早期应答基因可依据受试人群分组与给药阶段进行区分。此外，该类基因可将对乙酰氨基酚过量服用患者与对照组受试者清晰聚类分离，且能以100%的准确率预测暴露组别。此类应答基因可作为对乙酰氨基酚暴露的早期预警指标，其基因表达谱有望作为分子标志物供后续进一步研究评估。
研究整体设计：纳入因对乙酰氨基酚过量就诊于急诊室的患者。招募5名年龄在19至59岁之间的男性及女性受试者，其因对乙酰氨基酚过量服用后12小时至4天内就诊于急诊室。受试者的丙氨酸氨基转移酶（ALT）与天冬氨酸氨基转移酶（AST）水平升高，峰值分别超过400 U/I与120 U/I。分别在服药后2天或5天采集血液样本。