Abstract
Hypertension (HTN) affects about 1 billion people worldwide and the lack of a single identifiable cause complicates its treatment. Blood pressure (BP) levels are influenced by environmental factors, but there is a strong genetic component. Linkage analysis has identified several genes involved in Mendelian forms of HTN and the associated pathophysiological mechanisms have been unravelled, leading to targeted therapies. The majority of these syndromes are due to gain-of-function or loss-of-functions mutations, resulting in an alteration of mineralocorticoid, glucocorticoid, or sympathetic pathways. The diagnosis of monogenic forms of HTN has limited practical implications on the population and a systematic genetic screening is not justifiable. Genome-wide linkage and association studies (GWAS) have identified single nucleotide polymorphisms (SNPs), which influence BP. Forty-three variants have been described with each SNP affecting systolic and diastolic BP by 1.0 and 0.5 mmHg, respectively. Taken together Mendelian inheritance and all GWAS-identified HTN-associated variants explain 2–3% of BP variance. Epigenetic modifications, such as DNA methylation, histone modification and non-coding RNAs, have become increasingly recognized as important players in BP regulation and may justify a further part of missing heritability. In this review, we will discuss how genetics and genomics may assist clinicians in managing patients with HTN.
Highlights
Hypertension (HTN) is the most frequent modifiable risk factor for cardiovascular disease that affects about 1 billion people worldwide [1,2]
HSD11B2 gene promoter methylation is associated with HTN onset [58], as well as hypomethylation of genes of the renin-angiotensin-aldosterone (RAA) system or Na-K-Cl Co-transporter 1 (NKCC1) (Na-K-Cl co-transporter 1) gene respectively affect the response to Angiotensin-Converting Enzyme (ACE) inhibitors and diuretics [59,60]
Through these mechanisms the environment could influence genotype in each individual and these findings complicate the field of HTN genetics and genomics, adding another factor able to modify the phenotypic expression of patients with HTN [10]
Summary
Hypertension (HTN) is the most frequent modifiable risk factor for cardiovascular disease that affects about 1 billion people worldwide [1,2]. The identification of genes involved in Mendelian forms of HTN by linkage analysis and generation sequencing, with description of rare variants with a major impact on BP levels. This approach may identify the pathophysiological mechanism of a specific disorder and lead to a targeted therapy [7,8]. An approach based on families, twins and adopted children, or population studies using genome-wide linkage and association studies (GWAS). The latter can identify single nucleotide polymorphisms (SNPs), which influence the risk of developing high BP [8]. We selected the most relevant manuscripts pertinent to our review design, which comprised monogenic forms of hypertension, large-scale genome-wide associations studies, epigenetic modifications in hypertensive patients and pharmacogenomics
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