TY - JOUR

T1 - Mathematical modelling of the influence of ACE I/D polymorphism on blood pressure and antihypertensive therapy

AU - Kutumova, Elena

AU - Kovaleva, Anna

AU - Sharipov, Ruslan

AU - Lifshits, Galina

AU - Kolpakov, Fedor

N1 - Supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement 075-10-2021-093, Project CMB-RND-2123).

PY - 2024/5

Y1 - 2024/5

N2 - The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) 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 ACE I/D 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 ACE I/D 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 ACE I/D 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 ACE I/D 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.

AB - The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) 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 ACE I/D 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 ACE I/D 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 ACE I/D 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 ACE I/D 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.

KW - ACE I/D polymorphism

KW - Antihypertensive therapy

KW - Blood pressure regulation

KW - Cardiovascular system

KW - Mathematical modelling

KW - Renal system

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85191333791&origin=inward&txGid=c64868e438d54430e416b30cc5679011

UR - https://www.mendeley.com/catalogue/aded8a56-0c61-3b0d-85d4-a02f266a1cc8/

U2 - 10.1016/j.heliyon.2024.e29988

DO - 10.1016/j.heliyon.2024.e29988

M3 - Article

C2 - 38707445

VL - 10

JO - Heliyon

JF - Heliyon

SN - 2405-8440

IS - 9

M1 - e29988

ER -