Endocrine Abstracts

Introduction: MicroRNA (miRNA) has been shown to post-transcriptionally regulate physiological systems modulating blood pressure, including the adrenal biosynthesis of aldosterone. This raises the possibility that levels of specific miRNAs circulating in plasma might reflect these functional effects and have diagnostic value in the identification of hypertension and its various underlying causes. In a previous study, we measured plasma levels of miRNAs originating from the miR-24-1 cluster on chromosome 9, which correlated with the phenotype of patients with primary hypertension and primary aldosteronism. For this study, we have expanded our studies to measure a much larger array of 179 different circulating microRNAs in a population of 50 primary hypertensive patients, and assessed their correlation with relevant phenotypic traits, including systolic and diastolic blood pressure (SBP, DBP) and left ventricular mass index (LVMI).

Methods: Patients with primary hypertension (n=50) were drawn from the British Genetics of Hypertension (BRIGHT) study. Circulating miRNA was isolated from 200 μl EDTA plasma and analysed using Serum/Focus microRNA PCR panels (Exiqon), which employ simultaneous quantitative real-time PCR assays to measure 179 endogenous miRNAs and 13 control miRNAs. Statistical analysis was then used to identify correlation of miRNA level with phenotypic characteristics including systolic blood pressure (SBP), DBP, LVMI, age and BMI.

Results: Levels of 16 miRNAs correlated with either SBP and/or DBP (P<0.05). Of these, 2 miRNAs showing positive correlation with SBP or DBP, hsa-miR-28 and hsa-miR-1, were also found to correlate positively with left ventricular mass index (LVMI) in the 16 patients for whom we had this data (P<0.05). Interestingly, these miRNAs are each predicted to target mRNA transcribed from the CYP11B2 (aldosterone synthase) gene. Levels of hsa-miR-27b, which originates from the miR-24-1 cluster, positively correlated with age (P<0.05).

Conclusions: We have expanded our analysis of circulating miRNA levels in hypertension to encompass an array of 179 miRNAs in 50 patients. Several novel associations of circulating miRNAs with SBP, DBP, LVMI and BMI have been observed. Future work will concentrate on verifying these correlations, assessing their utility for diagnostic purposes, and identifying the mechanisms by which these miRNAs target expression of specific genes and exert phenotypic effects.