Novel estrogen receptor alpha promoter polymorphism increases ventricular hypertrophic response to hypertension

• Given the strong genetic contribution to blood pressure and left ventricular hypertrophy (LVH), and the influence of estrogen on these parameters, we hypothesized that polymorphisms in the estrogen receptor alpha (ERα) promoter may influence LVH. Three novel polymorphisms were identified upstream of the ERα alternatively spliced exon 1E, within sequence which demonstrated significant promoter activity in vitro. Demonstration of ERα E isoform expression in human ventricle by RT-PCR supported a possible functional role for the 1E novel polymorphisms in estrogen signaling in the heart. Indeed, G > A (-721 E) was significantly associated with LVH after controlling for systolic blood pressure and sex in a healthy population (n = 74), contributing to 23% of interventricular septum (IVS) width variance (p < 0.001) and 9.4% of left ventricular mass index (LVMI) variance (p = 0.035). In a separate hypertensive cohort, male carriers of the A allele (n = 8) had a 17% increase in IVS (95% CI: 6-28%) and a 19% increase in LVMI (3-34%) compared to GG homozygotes (n = 84). We conclude that a novel polymorphism in the promoter of a cardiac mRNA splice isoform of ERα is associated with LVH.

Nyckelord

Aldosterone

Gender differences

Genetic association studies

Hypertrophy/remodelling

Sex hormones

MEDICINE

MEDICIN

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)