The clinical application of UGT1A1 pharmacogenetic testing: Gene-environment interactions
The clinical application of UGT1A1 pharmacogenetic testing: Gene-environment interactions
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UGT1A1药物遗传学检测的临床应用：基因-环境相互作用
作者：
S. Marques;O. Ikediobi
在过去的十年中，药物遗传学试验的数量大大增加，使我们的临床应用知识的发展。尿苷二磷酸葡萄糖醛酸基转移酶1A 1基因（UGT 1A 1）试验是药物遗传学试验的一个示例。在UGT 1A 1中发现了许多变体，UGT 1A 1是胆红素和药物（如抗癌药物伊立替康）的主要结合酶。最近，美国食品药品监督管理局（FDA）建议检测UGT 1A 1 *28（一种与转录活性降低相关的等位基因）的存在，以预测患者是否存在伊立替康毒性风险。其他药物的给药-如UGT 1A 1酶的抑制剂-可以在临床上模拟 *28表型，而UGT 1A 1的诱导剂可以增加酶的葡萄糖醛酸化速率。*28多态性并非以相似的频率存在于所有种族中，这表明研究不同人群以确定UGT 1A 1 *28检测的临床相关性并识别其他临床相关的UGT 1A 1变体非常重要。生活方式等环境因素也会影响UGT 1A 1活性。这篇综述是对药物研究的关键分析，这些药物可能受到UGT 1A 1 *28的影响，这种多态性在地球仪的分布，在非洲和亚洲人群中可能具有临床意义的不同变体，以及生活方式如何影响依赖于UGT 1A 1活性的治疗结果。
Over the past decade, the number of pharmacogenetic tests has increased considerably, allowing for the development of our knowledge of their clinical application. The uridine diphosphate glucuronosyltransferase 1A1 gene (UGT1A1) assay is an example of a pharmacogenetic test. Numerous variants have been found in UGT1A1, the main conjugating enzyme of bilirubin and drugs such as the anticancer drug irinotecan. Recently, the US Food and Drug Administration (FDA) recommended testing for the presence of UGT1A1*28, an allele correlated with decreased transcriptional activity, to predict patients at risk of irinotecan toxicity. The administration of other drugs -- such as inhibitors of the UGT1A1 enzyme -- can clinically mimic the *28 phenotype, whereas inducers of UGT1A1 can increase the glucuronidation rate of the enzyme. The *28 polymorphism is not present in all ethnicities at a similar frequency, which suggests that it is important to study different populations to determine the clinical relevance of testing for UGT1A1*28 and to identify other clinically relevant UGT1A1 variants. Environmental factors such as lifestyle can also affect UGT1A1 activity. This review is a critical analysis of studies on drugs that can be affected by the presence of UGT1A1*28, the distribution of this polymorphism around the globe, distinct variants that may be clinically significant in African and Asian populations and how lifestyle can affect treatment outcomes that depend on UGT1A1 activity.
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影响因子：
11.2
作者：
Chantal Guillemette;R. Millikan;Beth Newman;David E. Housman
通讯作者：
Chantal Guillemette;R. Millikan;Beth Newman;David E. Housman
DOI：
10.1073/pnas.95.14.8170
发表时间：
1998-07-07
影响因子：
11.1
作者：
Beutler, E;Gelbart, T;Demina, A
通讯作者：
Demina, A
十字花科植物与 UGT1A1*28 多态性相互作用，以确定人类血清胆红素水平。
DOI：
10.1093/jn/135.5.1051
发表时间：
2005
期刊：
The Journal of nutrition
影响因子：
--
作者：
Peterson,Sabrina;Bigler,Jeannette;Horner,NeilannK;Potter,JohnD;Lampe,JohannaW
通讯作者：
Lampe,JohannaW
影响因子：
4.2
作者：
Saracino, Misty R.;Bigler, Jeannette;Schwarz, Yvonne;Chang, Jyh-Lurn;Li, Shiuying;Li, Lin;White, Emily;Potter, John D.;Lampe, Johanna W.
通讯作者：
Lampe, Johanna W.
影响因子：
45.3
作者：
Innocenti, F;Undevia, SD;Ratain, MJ
通讯作者：
Ratain, MJ