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Molecular Genetics of Human Hypertension: Role of Angiotensinogen¹

INSERM U36, Collège de France, 75005 Paris, France

I. Introduction

II. Structure of the AGT Gene

III. Characteristics of AGT

A. AGT as the substrate for renin

B. AGT as a member of the serpin superfamily: other roles for AGT?

IV. Tissue and Cellular Distribution

V. Regulation

A. Hormonal regulation of AGT

B. Regulation of AGT in disease

C. Regulation of AGT gene transcription

VI. Molecular Genetics of AGT in Human Essential Hypertension

A. Strategies

B. Linkage studies

C. Association studies of AGT polymorphism and high blood pressure

D. Pregnancy-induced hypertension

E. M235T variants, plasma AGT concentration, and blood pressure

F. Association of AGT variants with the renal blood flow response to Ang II infusion

VII. Molecular Genetics of AGT and Other Diseases

A. AGT variants and coronary heart disease

B. AGT variants and complications of diabetes

C. AGT, obesity, and blood pressure

VIII. Effects of AGT Gene Variants and Gene Targeting on Ang I Production and Blood Pressure

A. Human studies

B. Genetic studies in rats and mice

C. Genetic hypertension in rats

D. Antisense AGT oligodeoxynucleotides

E. Transgenic animals

F. AGT gene duplication

IX. Conclusions and Perspectives