Kutumova Elena, Kovaleva Anna, Sharipov Ruslan, Lifshits Galina, Kolpakov Fedor
Department of Computational Biology, Sirius University of Science and Technology, Sirius, Krasnodar region, Russia.
Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, Novosibirsk, Russia.
Heliyon. 2024 Apr 23;10(9):e29988. doi: 10.1016/j.heliyon.2024.e29988. eCollection 2024 May 15.
The angiotensin-converting enzyme (ACE) gene () insertion/deletion () polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between and the efficacy of inhibitors of the renin-angiotensin-aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited.
血管紧张素转换酶（ACE）基因的插入/缺失（I/D）多态性增加了个性化ACE抑制剂治疗的可能性，以在基因不同的亚组中优化其疗效并减少副作用。然而，其在这些亚组中的影响程度尚不清楚。因此，我们扩展了血压调节的计算模型，以研究I/D多态性对接受抗高血压治疗的人类血流动力学参数的影响。该模型表明，血压对血清ACE活性的依赖性是饱和度的函数，因此，I/D与血压水平之间缺乏关联可能是由于特定人群中ACE活性较高。此外，在一个模拟不同类抗高血压药物作用的扩展模型中，我们探讨了I/D与肾素-血管紧张素-醛固酮系统抑制剂疗效之间的关系。该模型预测，心血管和肾脏参数对治疗的反应直接取决于ACE活性。然而，仅在高ACE水平和低ACE水平的组之间观察到参数变化的显著差异，而同一组内不同的I/D基因型在绝对值上有相似的变化。我们得出结论，单一基因变异仅占治疗成功遗传因素的一小部分，其预测价值有限。
