CYP11B2 – Aldosterone Synthase
Aldosterone synthase is the enzyme that activates aldosterone. In fact, it is the only enzyme that can create aldosterone. Aldosterone synthase is encoded by the CYP11B2 gene on chromosome 8q22.2
The presence of left ventricular hypertrophy worsens the prognosis of cardiovascular disease 1, 2. In arterial hypertension, left ventricular structure is determined by hemodynamic (e.g., blood pressure) and nonhemodynamic factors such as angiotensin II 3, 4and aldosterone 5, 6, 7. Aldosterone stimulates cardiac collagen synthesis and thus contributes to the development of cardiac fibrosis 8, 9, 10. Aldosterone acts via the mineralocorticoid type I receptor, which has been found in both the rat heart 11, 12, 13and, more recently, in the human heart (14).
The human aldosterone synthase (CYP11B2) gene is located on chromosome 8, band 8q22, closely related to CYP11B1 15, 16. Gene variants of CYP11B2 have been associated with corticosterone methyloxidase II deficiency (17), and a chimeric 11-beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and arterial hypertension (18). One frequent polymorphism of the aldosterone synthase gene is located in the promoter region (−344 C/T). Another polymorphism is a gene conversion in intron 2 (19).
The −344 C/T polymorphism seems to be functionally relevant. Response to adrenocorticotropic hormone stimulation is reduced in the −344 CC genotype as compared with the TT genotype (20). Tetrahydroaldosterone excretion rate was found higher in the TT and CT genotypes than in the CC genotype (21). The C-allele has been found associated with elevated levels of plasma aldosterone, increased pulse wave velocity, and decreased baroreflex sensitivity 22, 23, but another study reports an elevated urinary aldosterone excretion in T-allele carriers (20). Blood pressure might also be influenced by the −344 C/T polymorphism. There are, however, inconsistent results about whether the T-allele 21, 24or the C-allele (20)is associated with arterial hypertension.
In a recent study, Kupari et al. (25)found an association between the −344 C/T polymorphism and left ventricular structure: the greater the number in C-alleles, the greater the left ventricular mass (LVM) and left ventricular end-systolic and end-diastolic diameter (25). In contrast, a most recent study by Schunkert et al. (26)could not confirm these findings in a larger study cohort. However, the pattern of cardiac morphology in subjects with the CC genotype in the study of Kupari et al. (25)is similar to that found in a state of volume load that can be the result of high dietary sodium intake 27, 28; consequently, a correlation between dietary sodium intake and LVM index was found in C-allele carriers only (25).
- Mol. Cell. Endocrinol. 217 (1–2): 67–74.
- Takeuchi, F., Yamamoto, K., Katsuya, T. et al. Reevaluation of the association of seven candidate genes with blood pressure and hypertension: a replication study and meta-analysis with a larger sample size. Hypertens Res 35, 825–831 (2012).
- Journal of the American College of Cardiology. 2001;37(3):878-884