Searching for Susceptibility Genes of Common Diseases: Approach to Essential Hypertension

Hypertension is one of the more common diseases affecting American adults. It is the cause of at least one fourth, and perhaps as many as one half, of all cardiovascular deaths. In spite of its importance, only about one half of those with the disease ordinarily are detected, only one half of those found to be hypertensive are being treated, and, of those who are receiving treatment, only one half, that is one eighth of the total hypertensive population, are receiving adequate treatment. Essential hypertension has been considered to be a disease of adults. The information available to physicians about its mechanisms, its endpoints, and its therapy has been developed from data collected in adult populations.

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Issues and Progress in Isolation of Susceptibility Genes of Essential Hypertension

Current Hypertension Reviews ◽

10.2174/1573402052952799 ◽

2005 ◽

Vol 1 (1) ◽

pp. 77-87 ◽

Cited By ~ 3

Author(s):

Tomohiro Nakayama

Keyword(s):

Essential Hypertension ◽

Susceptibility Genes

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Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang

PLoS ONE ◽

10.1371/journal.pone.0255311 ◽

2021 ◽

Vol 16 (7) ◽

pp. e0255311

Author(s):

Wenxi Jiang ◽

Xizi Wang ◽

Ronghui Li ◽

Panpan Wang ◽

Guangle Shan ◽

...

Keyword(s):

Essential Hypertension ◽

Transmembrane Domain ◽

Interaction Network ◽

Renin Angiotensin System ◽

Normal Subjects ◽

Susceptibility Genes ◽

Synonymous Mutations ◽

Han Nationality ◽

Target Capture ◽

Capture Sequencing

Essential hypertension is a common cardiovascular disease with complex etiology, closely related to genetic and environmental factors. The pathogenesis of hypertension involves alteration in vascular resistance caused by sympathetic nervous system (SNS) and renin angiotensin system (RAS). Susceptibility factors of hypertension vary with regions and ethnicities. In this study, we conducted target capture sequencing on 54 genes related to SNS and RAS derived from a collection of Han nationality, consisting of 151 hypertension patients and 65 normal subjects in Xinjiang, China. Six non-synonymous mutations related to hypertension were identified, including GRK4 rs1644731 and RDH8 rs1801058, Mutations are predicted to affect 3D conformation, force field, transmembrane domain and RNA secondary structure of corresponding genes. Based on protein interaction network and pathway enrichment, GRK4 is predicted to participate in hypertension by acting on dopaminergic synapse, together with interacting components. RDH8 is involved in vitamin A (retinol) metabolism and consequent biological processes related to hypertension. Thus, GRK4 and RDH8 may serve as susceptibility genes for hypertension. This finding provides new genetic evidence for elucidating risk factors of hypertension in Han nationality in Xinjiang, which in turn, enriches genetic resource bank of hypertension susceptibility genes.

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Angiotensinogen in Essential Hypertension: From Genetics to Nephrology

Journal of the American Society of Nephrology ◽

10.1681/asn.v123606 ◽

2001 ◽

Vol 12 (3) ◽

pp. 606-615

Author(s):

JEAN-MARC LALOUEL ◽

ANDREAS ROHRWASSER ◽

DANIEL TERREROS ◽

TERRY MORGAN ◽

KENNETH WARD

Keyword(s):

Genetic Variation ◽

Essential Hypertension ◽

Genetic Factors ◽

Genetic Alterations ◽

Loss Of Function ◽

Genetic Determinants ◽

Mendelian Disorders ◽

Common Diseases ◽

Physiologic Parameter ◽

Characteristic Features

Abstract. There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.

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