Effects of genetic variation in the aldosterone synthase (CYP11B2) gene on enzyme function.

Clinical Endocrinology
Christine D HollowayEleanor Davies

Abstract

Evidence suggests that high levels of aldosterone lead to hypertension and increased risk of cardiovascular disease. Around 15% of patients with essential hypertension have a raised aldosterone to renin ratio (ARR) suggesting that aldosterone production is inappropriately high in relation to its principal agonist angiotensin II. This may be due to increased activity of aldosterone synthase caused by genetic variation in the CYP11B2 gene. We screened the coding region of human CYP11B2 for genetic variants and tested their effects on function in vitro. Normotensive subjects (n = 69) were screened for sequence variants in the coding region of CYP11B2 by single-stranded conformation polymorphism (SSCP) analysis and sequencing. The effects of nonsynonymous variants on enzyme activity were assessed in JEG-3 cells transiently transfected with wild-type or variant expression plasmids. The conversion of the substrate 11-deoxycorticosterone (DOC) to corticosterone (B) and aldosterone was measured. Twenty variants were detected in CYP11B2 and eight analysed functionally (Arg87Gly, Asn281Thr, Gly288Ser, Lys296Asn, Asp335Asn, Gln404Arg, Ala414Pro and His439Tyr). Corticosterone synthesis was unaltered and aldosterone synthesis reduced in var...Continue Reading

References

Mar 1, 1978·Journal of Steroid Biochemistry·R Fraser, C P Lantos
Feb 1, 1995·Endocrine Research·P C White, L Slutsker
Mar 1, 1995·The Journal of Clinical Endocrinology and Metabolism·C E FardellaW L Miller
Apr 1, 1994·Clinical and Experimental Pharmacology & Physiology·R D GordonJ C Rutherford
Dec 1, 1996·The Journal of Clinical Endocrinology and Metabolism·C E FardellaW L Miller
May 19, 1997·Biochemical and Biophysical Research Communications·S NomotoY Shizuta
Nov 14, 1998·The Journal of Clinical Endocrinology and Metabolism·S Portrat-DoyenY Morel
Dec 18, 2001·Journal of Inorganic Biochemistry·N V BelkinaR Bernhardt
Feb 22, 2002·European Journal of Biochemistry·Stephanie BechtelRita Bernhardt
Sep 6, 2002·The Journal of Clinical Endocrinology and Metabolism·Pitt O LimJohn M C Connell
Apr 2, 2003·The New England Journal of Medicine·Bertram PittUNKNOWN Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators
Mar 18, 2004·Molecular and Cellular Endocrinology·Michael Lisurek, Rita Bernhardt
May 12, 2004·Molecular and Cellular Endocrinology·Mary H BassettWilliam E Rainey
May 12, 2004·Molecular and Cellular Endocrinology·Perrin C White
Jan 18, 2005·Lancet·Patricia M KearneyJiang He
Nov 24, 2006·Clinical Endocrinology·Marianne BarrEleanor Davies
Dec 5, 2006·Journal of Hypertension·Silvia SookoianCarlos Jose Pirola
Jul 25, 2007·Journal of Computer-aided Molecular Design·Luc RoumenJ J R Hermans
Jan 8, 2008·Molecular Genetics and Metabolism·Huy-Hoang NguyenRita Bernhardt

❮ Previous
Next ❯

Citations

Dec 4, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Lina SchifferRita Bernhardt
Dec 29, 2009·Biochimica Et Biophysica Acta·Christian DellesAnna F Dominiczak
Mar 1, 2010·Expert Review of Endocrinology & Metabolism·Mary C Ingram, Robert Fraser
Jan 6, 2017·American Journal of Hypertension·Erika S JonesBrian L Rayner
Jan 14, 2021·American Journal of Medical Genetics. Part a·Yaniv FaingelerntAbdulsalam Abu-Libdeh
May 21, 2021·The Journal of Biological Chemistry·Simoné Brixius-Anderko, Emily E Scott
Apr 27, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Diseases: Risk Factors

Cardiovascular disease is a significant health concern. Risk factors include hypertension, obesity, dyslipidemia and smoking. Women who are postmenopausal are at an increased risk of heart disease. Here is the latest research for risk factors of cardiovascular disease.

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.