Angiotensinogen in essential hypertension: from genetics to nephrology.
There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.
Lalouel
Jean-Marc
JM
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.|Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, Utah.
Rohrwasser
Andreas
A
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.
Terreros
Daniel
D
Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah.|Department of Veterans Affairs, Salt Lake City, Utah.
Morgan
Terry
T
Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.|Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
Ward
Kenneth
K
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah.
D000483:Alleles; D000804:Angiotensin II / Q000096:biosynthesis; D000808:Angiotensinogen / Q000235:genetics* / Q000502:physiology; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes; D006706:Homeostasis; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D007564:Japan; D008297:Male; D008957:Models, Genetic; D009399:Nephrons / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000150:complications / Q000235:genetics; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D012084:Renin-Angiotensin System / Q000502:physiology
D000808:Angiotensinogen; D000804:Angiotensin II