Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P348

SFEBES2009 Poster Presentations Steroids (37 abstracts)

−344 C/T polymorphism of aldosterone synthase gene (CYP11B2) and cortisol synthesis in heart failure patients

Ioannis Tsorlalis 1 , Robert Fraser 1 , Colette Jackson 1 , Mary Ingram 1 , Christine Holloway 1 , John McMurray 1 & John Connell 2

1BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; 2School of Medicine, University of Dundee, Dundee, UK.

Background: Increased levels of cortisol are associated with worse prognosis in heart failure (HF). The final step in cortisol production is catalysed by 11β-hydroxylase encoded by CYP11B1, which is highly homologous with CYP11B2. A common polymorphism in the aldosterone synthase gene (CYP11B2 −344T) is associated with a raised ratio of 11-deoxycortisol/ cortisol (S/F). We examined the relationship between −344C/T polymorphism and corticosteroid levels in decompensated and chronic HF.

Methods: Four hundred and fifty patients were studied during admission at hospital with decompensated HF and at a study visit 4 weeks after their discharge. Blood samples were collected on each occasion for corticosteroid and DNA analysis. Data were compared by the Wilcoxon and Mann–Whitney test between and within hospital and study visit respectively.

Results: Plasma cortisol concentration was higher and S/F was lower in the hospital than in the study visit (Table). Cortisol levels were not different between genotypes at hospital but 11-deoxycortisol levels and S/F were higher in TT than CC subjects. At study visit, cortisol levels were lower in TT subjects than other genotypes. 11-Deoxycortisol levels were not different between genotypes but the S/F ratio tended to be higher in TT patients reflecting the lower cortisol levels.

HospitalStudy visit
S (pmol/l) F (nmol/l)S/FS (pmol/l)F (nmol/l)S/F
All (n=450)490310*1.668*4672162.342
TT (n=115)591306*1.866*4871982.608
TC (n=234)486329*1.571*,†4832262.304
CC (n=101)405299*1.461*,†4302182.037
*P<0.05 versus study visit; P<0.05 versus TT (hospital); P<0.05 versus TT (study visit).

Conclusions: In decompensated HF, cortisol levels were not different between genotypes, but higher 11-deoxycortisol levels in TT subjects led to a raised S/F ratio. In chronic HF, cortisol levels were lower and S/F higher in TT subjects, consistent with reduced 11β-hydroxylation efficiency. Thus, in terms of cortisol exposure, TT may be a protective genotype in HF patients.

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