Alshogran Osama Y
a Department of Clinical Pharmacy, Faculty of Pharmacy , Jordan University of Science and Technology , Irbid , Jordan.
Expert Opin Drug Metab Toxicol. 2017 Oct;13(10):1063-1073. doi: 10.1080/17425255.2017.1376648. Epub 2017 Sep 9.
Genetic variation in metabolizing enzymes contributes to variable drug response and disease risk. Aldo-keto reductase type 1C (AKR1C) comprises a sub-family of reductase enzymes that play critical roles in the biotransformation of various drug substrates and endogenous compounds such as steroids. Several single nucleotide polymorphisms have been reported among AKR1C encoding genes, which may affect the functional expression of the enzymes. Areas covered: This review highlights and comprehensively discusses previous pharmacogenetic reports that have examined genetic variations in AKR1C and their association with disease development, drug disposition, and therapeutic outcomes. The article also provides information about the effect of AKR1C genetic variants on enzyme function in vitro. Expert opinion: The current evidence that links the effect of AKR1C gene polymorphisms to disease progression and development is inconsistent and needs further validation, despite of the tremendous knowledge available. Information about association of AKR1C genetic variants and drug efficacy, safety, and pharmacokinetics is limited, thus, future studies that advance our understanding about these relationships and their clinical relevance are needed. It is imperative to achieve consistent findings before the potential translation and adoption of AKR1C genetic variants in clinical practice.
代谢酶的基因变异会导致药物反应的差异和疾病风险。1C型醛糖酮还原酶（AKR1C）是还原酶家族的一个亚类，在各种药物底物和内源性化合物（如类固醇）的生物转化中起关键作用。在AKR1C编码基因中已报道了多个单核苷酸多态性，这可能会影响这些酶的功能表达。涵盖领域：本综述重点并全面讨论了以往的药物遗传学报告，这些报告研究了AKR1C中的基因变异及其与疾病发展、药物处置和治疗结果的关联。本文还提供了AKR1C基因变异对体外酶功能影响的相关信息。专家观点：尽管已有大量知识，但目前将AKR1C基因多态性的影响与疾病进展和发展联系起来的证据并不一致，需要进一步验证。关于AKR1C基因变异与药物疗效、安全性和药代动力学关联的信息有限，因此，需要开展进一步的研究，以增进我们对这些关系及其临床相关性的理解。在临床实践中潜在地转化和应用AKR1C基因变异之前，必须获得一致的研究结果。
