title: ACTH and Polymorphisms at Steroidogenic Loci as Determinants of Aldosterone Secretion and Blood Pressure.
abstract: The majority of genes contributing to the heritable component of blood pressure remain unidentified, but there is substantial evidence to suggest that common polymorphisms at loci involved in the biosynthesis of the corticosteroids aldosterone and cortisol are important. This view is supported by data from genome-wide association studies that consistently link the CYP17A1 locus to blood pressure. In this review article, we describe common polymorphisms at three steroidogenic loci (CYP11B2, CYP11B1 and CYP17A1) that alter gene transcription efficiency and levels of key steroids, including aldosterone. However, the mechanism by which this occurs remains unclear. While the renin angiotensin system is rightly regarded as the major driver of aldosterone secretion, there is increasing evidence that the contribution of corticotropin (ACTH) is also significant. In light of this, we propose that the differential response of variant CYP11B2, CYP11B1 and CYP17A1 genes to ACTH is an important determinant of blood pressure, tending to predispose individuals with an unfavourable genotype to hypertension.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. scott.mackenzie@glasgow.ac.uk.
authors.forename: Scott M
authors.initials: SM
authors.lastname: MacKenzie
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. marie.freel@glasgow.ac.uk.
authors.forename: E Marie
authors.initials: EM
authors.lastname: Freel
authors.affiliation: Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, UK. j.m.connell@dundee.ac.uk.
authors.forename: John M
authors.initials: JM
authors.lastname: Connell
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. robertfraser36@gmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Fraser
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. eleanor.davies@glasgow.ac.uk.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Davies
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000235:genetics*; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase
keywords: ACTH; CYP11B1; CYP11B2; CYP17A1; aldosterone; hypertension