Lakshmi Manasa Sakuntala Chekka

Title of Research: Plasma microRNA profiling reveals potential biomarkers of thiazide response

Additional Authors: T. Langaee; D. Wang; R. Rolf; A. Chapman; J. Gums; R. Cooper-DeHoff; J. Johnson


Thiazide diuretics (TZDs) are the 2nd most frequently prescribed class of antihypertensives. But <50% patients achieve target blood pressure (BP) on TZD monotherapy. Circulating microRNAs (miRNAs) are promising biomarkers often explored to predict disease and drug response and to tailor therapy to improve outcomes. Here we aim to identify plasma miRNAs associated with hydrochlorothiazide (HCTZ) response. We profiled 758 miRNAs in baseline (untreated) plasma samples of 36 uncomplicated hypertensive adults from the Pharmacogenomic Evaluation of Antihypertensive Responses clinical trial (18 Responders (R) and 18 Non-responders (NR) based on their diastolic BP response to HCTZ therapy), on TaqMan OpenArray Human microRNA panel using real-time qPCR. After appropriate quality control filtering and global normalization of expression data, differential expression analysis was performed using MannWhitney U test; ROC analysis for testing stability of miRNAs as biomarkers. Mean systolic/diastolic BP change in R vs NR was 14/10 vs 0/1 mmHg. Of those tested, 74 miRNAs were consistently expressed in plasma across samples, of which 10 were upregulated and 12 downregulated with >2-fold difference between R and NR. MiR-423-5p (fold change(fc)= 9.3, p=0.015), miR-134-5p (fc=8.6, p=0.03), miR-197-3p (fc=7.6, p=0.03), miR-193b-3p (fc=5.7, p=0.04) and miR-30e-3p (fc=0.2, p=0.04) were differentially expressed between R and NR, though none reached FDR adj p<0.05. ROC analysis showed AUC>0.72, p<0.05 for the above miRNAs. In this first ever genome-wide miRNA study of antihypertensive drug response, we discovered circulating miRNAs associated with BP response to HCTZ. Future studies are planned to validate these findings in a larger cohort, across different race group and across different TZD.


About the author

Lakshmi Manasa Sakuntala ChekkaI am Manasa Chekka, Final year PhD Candidate, working in the lab of Dr. Julie Johnson. My work is focused on cardiovascular pharmacogenomics and epigenomics, specifically focused on identifying circulating microRNA biomarkers that can predict patient response to thiazide diuretics, an anti-hypertensive medication.