Purpose of review: Modern molecular techniques are identifying pathways and genes involved in the pathogenesis of the complex disorder essential hypertension. This review provides an overview of genetic methodologies and recent results in the study of high blood pressure (BP), hypertension-attributed nephropathy, and related intermediate phenotypes.
Recent findings: Candidate gene studies have implicated aberrations in ion channels, ion channel regulation, aldosterone signaling, vasoconstriction and inflammation in essential hypertension; genome-wide association studies (GWAS) have detected more than 50 BP loci, most previously unsuspected in essential hypertension. Mapping by admixture linkage disequilibrium (MALD; or admixture mapping) recently led to a major breakthrough in hypertension-attributed kidney disease in African Americans, demonstrating the role of the apolipoprotein L1 (APOL1) and nonmuscle myosin heavy chain 9 (MYH9) genes in this primary kidney disease residing in the spectrum of focal segmental glomerulosclerosis. GWAS have detected associations between kidney function and UMOD and SHROOM3.
Summary: Genetic studies confirm that 'essential hypertension' consists of disparate mechanisms that ultimately lead to elevations in systemic BP. The cause of hypertension in the majority of cases remains unknown. It is anticipated that epigenetic phenomena, rare exonic mutations, and interactions with environmental factors make additional contributions.