Genetic and epigenetic factors of arterial hypertension: a bibliometric- and in-silico-based analyses

Abstract

Introduction: Arterial hypertension (AH) is a pervasive global health concern with multifaceted origins encompassing both genetic and environmental components. Previous research has firmly established the association between AH and diverse genetic factors. Consequently, scientists have conducted extensive genetic investigations in recent years to unravel the intricate pathophysiology of AH. Methods: In this study, we conducted a comprehensive bibliometric analysis employing VOSviewer software to identify the most noteworthy genetic factors that have been the focal point of numerous investigations within the AH field in recent years. Our analysis revealed genes and microRNAs intricately linked to AH, underscoring their pivotal roles in this condition. Additionally, we performed molecular docking analyses to ascertain microRNAs with the highest binding affinity to these identified genes. Furthermore, we constructed a network to elucidate the in-silico-based functional interactions between the identified microRNAs and genes, shedding light on their potential roles in AH pathogenesis. Results: Notably, this pioneering in silico examination of genetic factors associated with AH promises novel insights into our understanding of this complex condition. Our findings prominently highlight miR-7110-5p, miR-7110-3p, miR-663, miR-328-3p, and miR-140-5p as microRNAs exhibiting a remarkable affinity for target genes. These microRNAs hold promise as valuable diagnostic and therapeutic factors, offering new avenues for the diagnosis and treatment of AH in the foreseeable future. Conclusion: In summary, this research underscores the critical importance of genetic factors in AH and, through in silico analyses, identifies specific microRNAs with significant potential for further investigation and clinical applications in AH management.

Keywords: arterial hypertension; epigenetic factors; genetic factors; in silico analyses; miRNA.

FIGURE 1

Hypertension prevalence all over the world in 2010. The definition of prevalence of hypertension is systolic blood pressure≥140 mmHg or diastolic blood pressure≥90 mmHg or use of antihypertensive drugs in men and women. Data obtained from Mills et al. (2016).

FIGURE 2

Network visualization of the most frequent Mesh keywords that have examined in studies in which the roles of genetic factors in arterial hypertension (AH) are studied from 2018 to 2023. The size of each square of each MeSH keyword demonstrates the number of its occurrence.

FIGURE 3

Overlay visualization of the most frequent Mesh keywords that are examined in studies in which the roles of genetic factors in arterial hypertension (AH) have been studied since 2018.

FIGURE 4

2D structure of binding site between MicroRNA-7110-5p and 11 beta hydroxysteroid dehydrogenase type 1 (11β-HSD1), serotonin transporter (5-HTT), and D2-dopaminergic receptor (DRD2). Moreover, MiR-7110-3p has the most binding affinity to integrin subunit alpha 2I (ITGA2) and MicroRNA-663 and Angiotensinogen II Type 1 Receptor (AGTR1), Angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR), Apo lipoprotein E (APOE), Angiotensinogen II Type 1 Receptor (AGTR1), Angiotensin-converting enzyme (ACE), methylenetetrahydrofolate reductase (MTHFR), endothelin1 (EDN1) ring finger protein 213 (RNF213), Alpha-Adducin 1 (ADD1), and tumor necrosis factor (TNF), MiR-328-3p and vitamin D receptor (VDR), sodium channel epithelial 1 subunit alpha (SCNN1A) and angiotensinogen (AGT), MiR-140-5p and Hypoxia-inducible factor 1α (HIF1α). Each microRNA with its target genes are displayed and they are separated by a horizontal line. Red chains and green chains represent target gene and microRNA, respectively.

FIGURE 5

Various effects of microRNAs in the pathogenesis of AH. Blue and red arrows represent the effects of microRNAs on mechanisms that involve in AH and the impacts of these mechanisms on AH, respectively.

FIGURE 6

The network of action of microRNAs with the most tendency to genes that play a role in AH. MicroRNAs and genes are represented by green circles and light blue octagons, respectively. AH is located as an orange triangle in the center of figure.