Is Plasma Renin Activity Genetically Determined and How Much Does It Matter for Treating Hypertension?
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- essential hypertension
- genetic determinism
- Genome-Wide Association Study
- Kallikrein-Kinin System
- renin-angiotensin system
See Article by McDonough et al
Abundance of a protein in tissues or fluids is probably a quantitative genetic trait in most or even all cases. This can, however, be difficult recognizing and quantifying, depending on whether cellular or secreted proteins are considered and whether synthesis is mainly constitutive or also under the influence of potent physiological, lifestyle-related factors.
The issue can be exemplified by protein components of vasomotor peptide systems, renin–angiotensin, and kallikrein–kinin. Genetic determinism of angiotensin-converting enzyme (kininase II) level in plasma or kallikrein activity in urine has been recognized long ago, through familial transmission studies.1,2 Molecular basis for the genetic variability was documented later when gene structure became known.3,4 Genetic polymorphism of plasma angiotensinogen level has also been documented, in that case through genotype–phenotype association study and further gene studies addressing causality and mechanism.5,6
These cellular and secreted proteins, angiotensin-converting enzyme, kallikrein, and angiotensinogen are mainly synthesized constitutively, only submitted to mild hormonal influences. There is little or no interference of hemodynamic status and dietary factors with the effect of genetic background, explaining the observation of a strong heritable component of the population variance of plasma or urinary level in transmission and genomic association studies.7 What about renin?
Renin Level As a Genetic Trait?
Renin synthesis and secretion are largely modulated, acutely and chronically, by renal hemodynamic status, sympathetic nervous system activity, and sodium balance. Renin is synthesized as prorenin in various tissues, but prorenin is only activated in the kidney, in juxtaglomerular cells. Both prorenin and active renin are secreted in plasma. Measurement of active renin has both physiological and clinical relevance and is used, routinely for diagnosis of secondary forms of hypertension. Excess renin secretion is the primary cause of hypertension in renal artery stenosis, and deregulation of the renin-extracellular …