International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 42-53 http://medscipublisher.com/index.php/ijmms 42 Feature Review Open Access Genetic Mutations in Familial Hypertensive Heart Disease Huajun Chen1,2 1 Zhuji People's Hospital, Zhuji, 311800, Zhejiang, China 2 Zhuji Hospital ofWenzhou Medical University, Zhuji, 311800, Zhejiang, China Corresponding author: 303850911@qq.com International Journal of Molecular Medical Science, 2025, Vol.15, No.1 doi: 10.5376/ijmms.2025.15.0005 Received: 26 Dec., 2024 Accepted: 13 Feb., 2025 Published: 27 Feb., 2025 Copyright © 2025 Chen, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Chen H.J., 2025, Genetic mutations in familial hypertensive heart disease, International Journal of Molecular Medical Science, 15(1): 42-53 (doi: 10.5376/ijmms.2025.15.0005) Abstract Genetic factors play a critical role in the onset and progression of Familial Hypertensive Heart disease (FHH). Identifying key gene mutations and their functional impacts is essential for understanding the pathological mechanisms of the disease and developing personalized treatment strategies. This study summarizes the genetic basis of familial hypertensive heart disease, focusing on key gene mutations associated with the disease and their roles in regulating cardiac structure and function. It explores the relationship between gene mutations and disease mechanisms and evaluates their clinical potential in diagnosis, treatment, and prognosis management. The study reveals that mutations in genes such as MYH7, SCN5A, and AGTare closely linked to myocardial hypertrophy, arrhythmias, and abnormalities in blood pressure regulation, respectively. Mutations in ion channel genes significantly affect myocardial fibrosis and electrical conduction abnormalities. This study systematically reviews FHH-related gene mutations and mechanisms, providing valuable insights for molecular diagnosis, biomarker development, and therapeutic target identification. Additionally, it emphasizes the importance of integrating genetics, epigenetics, and multi-omics data to accelerate the translation from basic research to precision medicine, offering more effective personalized interventions for FHH patients. Keywords Familial hypertensive heart disease; Gene mutations; Epigenetics; Precision medicine; Personalized therapy 1 Introduction Familial Hypertensive Heart Disease (FHH) is a hereditary condition characterized by elevated blood pressure and associated cardiovascular complications. It is often inherited in an autosomal dominant manner, meaning that a single copy of the mutated gene from either parent can cause the disorder. FHH can lead to severe health issues, including heart failure, stroke, and kidney disease, making it a significant concern for affected families (Solomon et al., 1990; Bassat et al., 2017). Genetic factors play a crucial role in the development and progression of hypertensive heart disease. Mutations in specific genes can disrupt normal physiological processes, leading to hypertension and its associated complications. For instance, mutations in the WNK1, WNK4, CUL3, and KLHL3 genes have been identified as causative factors in Familial Hyperkalemia and Hypertension (FHHt), a related condition characterized by hyperkalemia and hypertension (Bassat et al., 2017; Shirin et al., 2023). Similarly, mutations in the Bone Morphogenetic Protein Receptor-II gene (BMPR2) have been linked to familial primary pulmonary hypertension, highlighting the diverse genetic underpinnings of hypertensive disorders (Deng et al., 2000). Identifying key gene mutations is crucial for uncovering the mechanisms underlying hypertensive heart disease and developing personalized treatment strategies. Understanding the specific genetic mutations involved can help in predicting disease risk, tailoring interventions, and improving patient outcomes. For example, the identification of a new recessive mutation in the KLHL3 gene (S553L) in a family with FHHt has provided insights into the disease's inheritance patterns and potential therapeutic targets (Bassat et al., 2017). Similarly, recognizing mutations in the LDL receptor gene (LDLR) has been instrumental in managing familial hypercholesterolemia, a condition that often coexists with hypertensive heart disease (Austin et al., 2004; Gidding et al., 2015). This study aims to summarize the gene mutations and their functional impacts in Familial Hypertensive Heart disease (FHH) and explore potential research directions and clinical applications. Additionally, it analyzes genetic
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