Searchable abstracts of presentations at key conferences in endocrinology

ea0019p305 | Steroids | SFEBES2009

Differences in aldosterone synthase and 11β-hydroxylase genes between Caucasian and Afro-Caribbean hypertensive families

Alvarez-Madrazo S , Padmanabhan S , Friel E , McKenzie C , Keavney B , Davies E , Connell J

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are highly homologous in their coding regions (95%), lie in tandem approximately 40kb apart in human chromosome 8, and may have arisen from gene duplication. The pattern of linkage disequilibrium (LD) of this region in a population is determined not only by the distribution of recombination events but also by demographic factors determining the amount of random genetic drift. There is suggestiv...

ea0005p233 | Steroids | BES2003

In vitro synthesis of 18-hydroxycortisol (18-OH-F) and 18-oxocortisol (18-oxo-F); clues to their origin in normal human subjects

Shakerdi L , Friel E , Davies E , Connell J , Wallace A , Fraser R

INTRODUCTIONThe plasma concentrations and urinary excretion rates of 18-OH-F and 18-oxo-F are high in Conn's syndrome and glucocorticoid suppressible hyperaldosteronism, reputedly because aldosterone synthase (AS) has abnormal access to cortisol (F). However, both compounds are also excreted in normal subjects. Two enzymes, 11beta-hydroxylase (11OH) and AS, located in the zona fasiculata (ZF) and zona glomerulosa (ZG) respectively, are capable of 18-hydroxylation but only ...

ea0002oc4 | Vascular and Metabolic | SFE2001

The SF1 site polymorphism of the aldosterone synthase gene (CYP11B2) influences urinary steroid production and pressor dose response to angiotensin II during dietary manipulation of the renin-angiotensin system

Kennon B , Davies E , Ingram M , Friel E , Anderson N , Fraser R , Connell J

Background: A polymorphism within the CYP11B2 gene, characterised by a C/T substitution at position 344, the putative binding site for steroidogenic transcription factor1, has been shown to influence aldosterone excretion rate and blood pressure in essential hypertension.Aims: Assess the effect of contrasting genotype for the SF1 site on urinary and plasma steroid production during dietary manipulation of the renin-angiotensin system and assess the press...

ea0002oc13 | Neuroendocrinology | SFE2001

Transcription of corticosteroidogenic genes in human cerebellum and hippocampus

MacKenzie S , Friel E , Fraser R , Seckl J , Connell J , Davies E

In the rat hippocampus, corticosteroids modulate neuronal excitability. Glucocorticoid excess within the rat hippocampus results in a neurodegenerative effect, although corticosteroids also protect oligodendrocytes from cytokine-mediated apoptosis. Other studies have shown that systemically insignificant levels of aldosterone affect systemic blood pressure when administered icv. Previously, we have shown by RT-PCR and immunohistochemistry that the genes for 11beta-hydroxylase ...

ea0008oc22 | Young Endocrinologist Session | SFE2004

Effect of Variation at the Aldosterone Synthase Locus (CYP11B2) on Adrenal 11-beta hydroxylation: Pilot Data from the MRC BRIGHT Study

Freel M , McKenzie S , Friel E , Ingram M , Davies E , Fraser R , Dominiczak A , Caulfield M , Connell J

Aldosterone is an important cardiovascular hormone. Around 15 % of hypertensives have alteration in aldosterone regulation, defined by a raised ratio of aldosterone to renin (ARR). Studies of CYP11B2, the aldosterone synthase gene, focus on a single nucleotide polymorphism in the 5'promotor region (-344 C/T). We have shown that the T allele is associated with increased urinary excretion and plasma levels of aldosterone and is more common amongst hypertensives with a raised ARR...

ea0019oc11 | Neuroendocrine and Steroids | SFEBES2009

Familial and phenotypic associations of the aldosterone renin ratio in the general population

Alvarez-Madrazo S , Padmanabhan S , Wallace M , Campbell M , Smith J , Friel E , Dorrian C , Keavney B , Davies E , Connell J

Recent studies in non-hypertensive patients have shown aldosterone renin ratio (ARR) to be heritable and associated with increased risk of blood pressure (BP) elevation. Furthermore, a raised ARR is present in 10% of hypertensive patients although the precise significance of this is unclear. The magnitude of heritability of ARR will indicate the influence of genetic determination of the phenotype. In this study, we estimated the heritabilities of the components of ARR and the ...

ea0011oc44 | Endocrine genetics | ECE2006

Functional impact of polymorphic variation in the gene encoding 11β-hydroxylase (CYP11B1): reduced adrenal 11-hydroxylase efficiency identifies a key intermediate phenotype in hypertension

Barr M , Friel E , MacKenzie SM , Holloway CD , Freel EM , Brain NJR , Wilkinson DM , Ingram M , Fraser R , Dominiczak AF , Connell JMC , Davies E

The regulation of aldosterone secretion is altered in essential hypertension: the phenotype of relative aldosterone excess is present in up to 15% of subjects. The gene encoding aldosterone synthase (CYP11B2) offers an obvious candidate to account for this and a polymorphism in its 5′ untranslated region (UTR; −344C/T) is associated with increased frequency of hypertension and higher aldosterone levels. However, this variation is more closely associated with...