The impact of renin-angiotensin system polymorphisms on physiological and pathophysiological processes in humans

The renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic f...

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Vydáno v:Current opinion in nephrology and hypertension Ročník 13; číslo 1; s. 101
Hlavní autoři: Miller, Judith A, Scholey, James W
Médium: Journal Article
Jazyk:angličtina
Vydáno: England 01.01.2004
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ISSN:1062-4821
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Abstract The renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic factors that influence the genotype-phenotype correlation. A common variant of the angiotensinogen gene (T235) predicts elevated levels of circulating angiotensinogen, and polymorphisms of this gene have been linked to physiologic responses and to the risk of cardiovascular disease. The angiotensin-converting-enzyme gene insertion/deletion polymorphism, although not considered functional, has been associated with physiologic responses and disease risk in hypertension and diabetes. A polymorphism of the angiotensin type 1 receptor gene, A1166C, has been the focus of several physiologic studies. These authors will focus on mechanistic studies in normal humans and those with diabetes mellitus or hypertension that examine the impact of these polymorphisms on physiologic responses. Recent studies provide divergent results. Many have shown that mediating factors interfere with the genotype-phenotype correlation. Studies in normal individuals and in those with diabetes mellitus have shown that sodium status and glycemia can alter the impact of genotype. In individuals with essential hypertension, the pathway between genotype and physiology can be disrupted by gender and/or race. Divergent results in many studies may be attributable to various non-genomic and environmental influences on the pathway between gene polymorphism and physiology. Clarification of these factors should allow a better understanding of genotype-phenotype correlation.
AbstractList The renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic factors that influence the genotype-phenotype correlation. A common variant of the angiotensinogen gene (T235) predicts elevated levels of circulating angiotensinogen, and polymorphisms of this gene have been linked to physiologic responses and to the risk of cardiovascular disease. The angiotensin-converting-enzyme gene insertion/deletion polymorphism, although not considered functional, has been associated with physiologic responses and disease risk in hypertension and diabetes. A polymorphism of the angiotensin type 1 receptor gene, A1166C, has been the focus of several physiologic studies. These authors will focus on mechanistic studies in normal humans and those with diabetes mellitus or hypertension that examine the impact of these polymorphisms on physiologic responses. Recent studies provide divergent results. Many have shown that mediating factors interfere with the genotype-phenotype correlation. Studies in normal individuals and in those with diabetes mellitus have shown that sodium status and glycemia can alter the impact of genotype. In individuals with essential hypertension, the pathway between genotype and physiology can be disrupted by gender and/or race. Divergent results in many studies may be attributable to various non-genomic and environmental influences on the pathway between gene polymorphism and physiology. Clarification of these factors should allow a better understanding of genotype-phenotype correlation.
The renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic factors that influence the genotype-phenotype correlation. A common variant of the angiotensinogen gene (T235) predicts elevated levels of circulating angiotensinogen, and polymorphisms of this gene have been linked to physiologic responses and to the risk of cardiovascular disease. The angiotensin-converting-enzyme gene insertion/deletion polymorphism, although not considered functional, has been associated with physiologic responses and disease risk in hypertension and diabetes. A polymorphism of the angiotensin type 1 receptor gene, A1166C, has been the focus of several physiologic studies. These authors will focus on mechanistic studies in normal humans and those with diabetes mellitus or hypertension that examine the impact of these polymorphisms on physiologic responses.PURPOSE OF REVIEWThe renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully elucidated. Physiologic genomics continues to be an active area of research that emphasizes definition of phenotype and clarification of non-genomic factors that influence the genotype-phenotype correlation. A common variant of the angiotensinogen gene (T235) predicts elevated levels of circulating angiotensinogen, and polymorphisms of this gene have been linked to physiologic responses and to the risk of cardiovascular disease. The angiotensin-converting-enzyme gene insertion/deletion polymorphism, although not considered functional, has been associated with physiologic responses and disease risk in hypertension and diabetes. A polymorphism of the angiotensin type 1 receptor gene, A1166C, has been the focus of several physiologic studies. These authors will focus on mechanistic studies in normal humans and those with diabetes mellitus or hypertension that examine the impact of these polymorphisms on physiologic responses.Recent studies provide divergent results. Many have shown that mediating factors interfere with the genotype-phenotype correlation. Studies in normal individuals and in those with diabetes mellitus have shown that sodium status and glycemia can alter the impact of genotype. In individuals with essential hypertension, the pathway between genotype and physiology can be disrupted by gender and/or race.RECENT FINDINGSRecent studies provide divergent results. Many have shown that mediating factors interfere with the genotype-phenotype correlation. Studies in normal individuals and in those with diabetes mellitus have shown that sodium status and glycemia can alter the impact of genotype. In individuals with essential hypertension, the pathway between genotype and physiology can be disrupted by gender and/or race.Divergent results in many studies may be attributable to various non-genomic and environmental influences on the pathway between gene polymorphism and physiology. Clarification of these factors should allow a better understanding of genotype-phenotype correlation.SUMMARYDivergent results in many studies may be attributable to various non-genomic and environmental influences on the pathway between gene polymorphism and physiology. Clarification of these factors should allow a better understanding of genotype-phenotype correlation.
Author Miller, Judith A
Scholey, James W
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Snippet The renin-angiotensin system plays a central role in health and disease but the determinants of renin-angiotensin system activity have not been fully...
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SubjectTerms Angiotensinogen - genetics
Animals
Gene Deletion
Humans
Polymorphism, Genetic - physiology
Receptor, Angiotensin, Type 1 - genetics
Receptor, Angiotensin, Type 1 - physiology
Renin-Angiotensin System - genetics
Title The impact of renin-angiotensin system polymorphisms on physiological and pathophysiological processes in humans
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