Genetics of the renin-angiotensin system in human hypertension

Most of human hypertension is deemed ‘essential’, an euphemism reflecting lack of knowledge about its etiology. Difficult to define, and of unclear clinical specificity, hypertension admits a genetic component and is commonly labeled a polygenic disease. As such, it could qualify as a geneticistʹs nightmare to the same extent as diabetes mellitus. because a variety of observations support etiological heterogeneity, however, it is reasonable to assume that some genetic determinants may exert predominant effects in the development of at least some forms of essential hypertension. Given the critical role of the renin-angiotensin system in vascular tone and plasma volume control, every component of this system has the potential of being involved in the development of hypertension. While there is little evidence for an involvement of other components of the system, we will review data on angiotensinogen, the substrate of renin, which suggest that molecular variants at this locus may predispose to some forms of hypertension, either in pregnancy or later in life.