Molecular Genetics of Polygenic Hypertension

Contrasting to rare monogenic forms of hypertension, essential hypertension is the most clinically diagnosed ailment leading to high morbidity and mortality; however, its underlying mechanisms continue to be undeciphered. To assist this endeavor, investigations utilizing rodent models have revealed multiplex genetic architecture for quantitative trait loci (QTLs), for blood pressure (BP), elaborate QTL–QTL interactions and efficacious genome regulations of QTL functions. Although BP is a quantitatively measured trait manifesting in a continuous variation, each QTL governing it appears to behave as an independent and ‘monogenic’ Mendelian determinant. Some QTLs are functionally modularized by epistasis that implies a common pathway or cascade; whereas others belong to parallel epistatic modules. These insights suggest that similar genetic mechanisms probably shepherd the genetic architecture for essential hypertension. Translation of gene discovery to therapeutic targets and diagnostic tools will require a consolidation of functional validation of genes in animal models with association studies in targeted human populations.

 

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Key Concepts

The quantitative governance of blood pressure variations is realized by several genes or quantitative trait loci (QTLs). Each QTL can operate autonomously and comports in a ‘monogenic’ pattern. Those QTLs that occur to mutually conceal their BP effects can be epistatically modularized, consequently, solving the conundrum of overabundant QTLs in the genome. Despite the puissance of QTLs, potent genome regulations can disallow QTLs to influence blood pressure (BP). In both human and animal association/linkage studies, population-dependence and the influence of genome heterogeneity on exhibiting the amplitude of BP effect are frequently observed occurrences.

Keywords: quantitative trait loci; blood pressure; positional cloning; candidate genes

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Deng, Alan Y(Sep 2008) Molecular Genetics of Polygenic Hypertension. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021466]