Tailored Therapy of ACE Inhibitors in Stable Coronary Artery Disease: Pharmacogenetic Profiling of Treatment Benefit

Abstract

Angiotensin-converting enzyme (ACE) inhibitors are among the most commonly used drugs in stable coronary artery disease as these agents have been proven to be effective for reducing the risk of cardiovascular morbidity and mortality. As with other drugs, individual variation in treatment benefit is likely. Such heterogeneity could be used to target ACE-inhibitor therapy to those patients most likely to benefit from treatment. However, prior attempts to target ACE-inhibitor therapy to those patients who are most likely to benefit of such prophylactic treatment in secondary prevention using clinical characteristics or the level of baseline risk appeared not to be useful. A new approach of 'tailored therapy' could be to integrate more patient-specific characteristics, such as the genetic information of patients. Pharmacogenetic research of ACE inhibitors in coronary artery disease patients is at a formative stage, and studies are limited. The Perindopril Genetic association (PERGENE) study is a large pharmacogenetic substudy of the randomized placebo-controlled European trial On Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery disease (EUROPA) trial, aimed to assess the feasibility of pharmacogenetic profiling of ACE-inhibitor therapy by perindopril. This article summarizes the recent findings of the PERGENE study and pharmacogenetic research of the treatment benefit of perindopril in stable coronary artery disease.

Interactions of Renin–angiotensin System Gene Polymorphisms and Antihypertensive Effect of Benazepril in Chinese Population

“…These results suggest we should find a way to consider haplotypes and interactions simultaneously in future studies and more RAS genes, including ACE, renin (REN) and aldosterone synthase gene (CYP11B2) can be taken into analysis so that the pharmacogenomics of RAS can be understood more completely. This idea would also be suitable for other pathways suspected to influence ACEI therapy effect, such as the kallikrein-bradykinin system [13]. Genotyping of some of these genes is in progress in our study.…”

“…Both AngII and ACE2 could regulate the homeo-II and ACE2 could regulate the homeoand ACE2 could regulate the homeostasis of cardiovascular system by binding to angiotensin II receptor 1 (AGTR1), so AGTR1 may also be involved in ACEIs' blood pressure reduction mechanism. A number of pharmacogenetic studies have been performed to test whether polymorphisms from these genes contribute to the antihypertensive effect of ACEIs, with few confirmed results [7][8][9][10][11][12][13]. Among these studies, few have considered gene-gene interactions in RAS.…”

Stroke Pharmacogenetics

“…In 5,688 with prior stroke or TIA, the presence of the ACE genotype was not found to modify the BP response to perindopril [ 153 ] . Similarly, in two large cohorts (8,907 with stable CAD and 3,571 with cerebrovascular disease), no signi fi cant association between genetic determinants of the renin-angiotensin-aldosterone system and BP response to perindopril were identi fi ed, despite several SNPs highlighted as being associated with hypertension [ 154 ] . Future, long-term large-scale studies focusing on both ACE inhibitor polymorphisms and associated interlinking pathways are required to delineate the relationship between serum ACE levels and ACE inhibitor ef fi cacy.…”

Применение Фармакогенотипирования И дозирование Некоторых Препаратов В Урологии И нефрологии

“…Лизиндецифитарная протеинки-наза (WNK) регулирует совместный тиазидчувстви-тельный натрий-хлоридный транспорт в дистальном нефроне. Мутации в 2 видах генов этого семейства -WNK1 и WNK4 приводят к синдрому Гордона -се-мейной гиперкалиемической гипертензии [25]. Для трех однонуклеотидных полиморфизмов генов в WNK1-гене (rs2107614, rs1159744, rs2277869) показа-на существенная ассоциация между снижением ар-териального давления и приемом гидрохлортиазида.…”