Is There a Role for Genomics in the Management of Hypertension?

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.

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima–media thickness: A longitudinal twin study

“…However, the genetic determinants are probably highly heterogeneous, which poses exceptional challenges to identification of the underlying genes. Burello et al [36] described 43 single-nucleotide polymorphisms (SNP) variants, in a recent GWAS study, with each SNP affecting SBP and DBP by 1.0 and 0.5 mmHg, respectively. In 2017 one of the largest GWAS research studies to this date, that used the 1000 Genomes Project-based imputation in 150,134 European ancestry individuals reported 8 loci of the genome not previously connected to BP regulation and increasing the number of genes to 48 as candidates for priority follow-up [37].…”

“…In 2017 one of the largest GWAS research studies to this date, that used the 1000 Genomes Project-based imputation in 150,134 European ancestry individuals reported 8 loci of the genome not previously connected to BP regulation and increasing the number of genes to 48 as candidates for priority follow-up [37]. Epigenetic changes, such as DNA methylation, histone modification and non-coding RNAs, have been increasingly recognized as important players in BP regulation and may justify a further part of missing heritability [36]. However, to this end, the longitudinal role of these effects on BP heritability remained unclear.…”

Genetic Programming of Hypertension

“…The gene responsible for FH type II remains unknown and, therefore, diagnosis is usually challenging and based on exclusion of other conditions. Treatment of FH type II consists of administration of mineralocorticoid receptor antagonists and/or unilateral adrenalectomy for aldosterone-producing adenomas ( 14 ).…”

“…This mutated channel allows excess calcium entry into the adrenal glomerulosa cells and subsequent hyperaldosteronism ( 16 ). Mineralocorticoid receptor antagonists may be used for the treatment of FH type IV ( 14 ).…”

Premature Stroke Secondary to Severe Hypertension Results from Liddle Syndrome Caused by a Novel SCNN1B Mutation

“…Hypertension affects approximately 1 billion people worldwide [1] and it is the most prevalent risk factor for cardiovascular diseases and related disabilities [2]. A minority of patients with hypertension have an inherited disorder, and monogenic hypertension syndromes are specific types of secondary hypertension [3, 4]. Among these diseases, Liddle syndrome (LS) is relatively rare, and the prevalence of LS across the general hypertensive population is unknown.…”