Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain.
Pharmacogenet Genomics. 2011 Jul;21(7):357-64. doi: 10.1097/FPC.0b013e328346d2bb.
The existence of genetic polymorphisms in metabolizing enzymes can be regarded as one of the principal causes of interindividual variation in response to drugs and adverse reactions. In the case of enzyme CYP2C9, the presence of genetic coding variants could be considered a risk factor for suffering from gastrointestinal haemorrhages associated with the use of nonsteroidal anti-inflammatory drugs, due to a reduction in the enzyme's rate of metabolism. The aim of this study was to conduct a systematic critical review aimed at assessing whether the presence of CYP2C92 and CYP2C93 could increase the risk of suffering from gastrointestinal haemorrhages due to nonsteroidal anti-inflammatory drug use. Using MEDLINE as the data source, the search was limited to scientific studies published in English. Six studies met the inclusion criteria, whereas three reported no results because there were no homozygous mutant genotypes for CYP2C92 and 3 in their samples, risk of bleeding was associated by one with the presence of CYP2C92 and by two with the CYP2C93 coding variant. Some of the studies included in this review contained methodological limitations, which prevented the increased risk of suffering gastrointestinal haemorrhages due to nonsteroidal anti-inflammatory drug use from being satisfactorily linked to the presence of CYP2C9 coding variants.
代谢酶中遗传多态性的存在可以被视为导致药物反应和不良反应个体间差异的主要原因之一。在酶 CYP2C9 的情况下,由于酶代谢率降低,存在遗传编码变异可以被认为是非甾体抗炎药相关胃肠道出血的危险因素。本研究旨在进行系统的批判性评价,以评估 CYP2C92 和 CYP2C93 的存在是否会增加非甾体抗炎药使用引起胃肠道出血的风险。使用 MEDLINE 作为数据源,搜索仅限于发表在英语中的科学研究。有六项研究符合纳入标准,而有三项研究因为其样本中没有 CYP2C92 和3 的纯合突变基因型,所以没有结果,风险出血与 CYP2C92 的存在相关,与 CYP2C93 编码变异相关的有两项。本综述中包含一些方法学局限性的研究,这些局限性使得非甾体抗炎药使用引起胃肠道出血的风险增加与 CYP2C9 编码变异之间无法得到令人满意的联系。