Genetic factors associated with volume-sensitive hypertension.
Defining the genetic basis of essential hypertension is most informative when the blood pressure regulation is correlated with physiologic mechanisms, e.g., responses of the renin-angiotensin aldosterone system (RAAS) in hypertensive subjects. The aldosterone response to angiotensin II (Ang II) on a low salt diet is influenced by gender, plasma renin activity, and most significantly, familial resemblance, but only in males and in post-menopausal females. There is familial aggregation of low-renin hypertension, no association with candidate genes of the RAAS, but, a highly significant association with polymorphisms in the alpha-adducin gene. Finally, angiotensinogen (AGT) genotype effects renal and adrenal responses to Ang II in patients with hypertension. These results strongly suggest that in contrast to population-based studies that use hypertension as the phenotype, classifying patients by the variability in physiologic, mechanistic traits enhances the probability of identifying the genetic factors influencing a rise in blood pressure.
Williams
Gordon H
GH
Endocrinology, Diabetes and Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, RFB-2, Boston, MA 02115, USA. gwilliams@partners.org
D000367:Age Factors; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage; D000808:Angiotensinogen / Q000235:genetics; D001810:Blood Volume; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004039:Diet, Sodium-Restricted; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012737:Sex Factors; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D000099291:Adducins
D000450:Aldosterone; D000804:Angiotensin II; D000808:Angiotensinogen; D002148:Calmodulin-Binding Proteins; D012083:Renin; D014662:Vasoconstrictor Agents; D000099291:Adducins