Third Department of Internal Medicine, Fukui University School of Medicine, Matsuokashimoaizuki, Eiheiji, Japan.
Curr Hypertens Rep. 2011 Oct;13(5):356-61. doi: 10.1007/s11906-011-0212-0.
The concept of "pharmacogenomics" or "pharmacogenetics" promises to offer the ultimate in personalized medicine, and the renin-angiotensin system (RAS) is one of the most plausible candidates for the application of this approach in the area of hypertension. For the past two decades, genetic variants of the RAS have been tested for association with blood pressure response, but the results have been inconsistent. The problems have been attributed to many issues, but the most fundamental concern is thought to be the statistical power of the studies. Therefore, we have tried to put together a new systematic review using a database search including only recent reports with adequate numbers of subjects, and 11 reports were identified. From the results, we were able to draw conclusions with nearly consistent findings that the conventional genetic variants of the system (i.e., the ACE I/D, AGT M235T, AT1 A1166C, and AT2 variant) are not associated with antihypertensive effects by RAS blockade, at least by one individual SNP. By contrast, significant associations have been reported (by one report each) for AGT rs7079, AT1 haplotype, REN, and ACE2. For these variants, further evaluations and confirmation are anticipated.
“药物基因组学”或“药物遗传学”的概念有望提供终极的个性化医疗，肾素-血管紧张素系统（RAS）是在高血压领域应用这种方法的最合理候选者之一。在过去的二十年中，已经测试了 RAS 的遗传变异与血压反应的关联，但结果不一致。这些问题归因于许多问题，但最根本的问题被认为是研究的统计效力。因此，我们试图使用仅包括最近报告且具有足够数量的受试者的数据库搜索来进行新的系统评价，共确定了 11 份报告。从结果中，我们能够得出结论，几乎一致的发现表明，该系统的常规遗传变异（即 ACE I/D、AGT M235T、AT1 A1166C 和 AT2 变体）与 RAS 阻断的降压作用无关，至少与一个个体 SNP 无关。相比之下，已经报道了（每个报告各有一个）AGT rs7079、AT1 单倍型、REN 和 ACE2 的显著关联。对于这些变体，预计将进行进一步的评估和确认。
