Abstract 11404: MicroRNA Associated with Atherogenic Dyslipidemia In South Asian Men

Abstract

BACKGROUND MicroRNA are an epigenetic post-transcriptional regulatory mechanism of messenger RNA translation, and are potential biomarkers of pathophysiology and response to interventions. MicroRNA in human blood are differentially expressed in numerous disease conditions, and in vitro studies indicate that microRNA play a role in regulation of lipoprotein metabolism. South Asians have a high prevalence of dyslipidemia and disproportionate excess cardiovascular disease. The aim of this study was to measure miR expression in blood of South Asians with and without dyslipidemia.

METHODS Peripheral blood was obtained by venipuncture following 10-hour fast. Lipoprotein fractionation was performed by calorimetry. Cases (n = 22) had HDL-c < 40mg/dL and triglycerides > 150mg/dL, whereas controls (n = 22) had neither. MicroRNA were isolated from whole blood and pooled by case/control status. Array-based measurement of 85 microRNA was performed on pools, followed by validation of select microRNA targets in individual samples by quantitative polymerase chain reaction (qPCR).

RESULTS Of the 85 microRNA represented on the array, 74 were detected with sufficient precision to meet a priori quality control criteria. Three (miR-214, miR-885-5p, miR-205) displayed increased expression in cases compared to controls. Sixteen (miR-100, miR-374a, miR-7, miR-18a, miR-125b, miR-148a, miR-17, miR-221, miR-21, miR-93, miR-143, miR-17*, miR-96, miR-106b, miR-103a, miR-20a) displayed at least two-fold (range 2.0 [[Unable to Display Character: &#8211;]] 2.9) decreased expression (p < 0.05) in cases compared to controls. Three microRNA (miR-106b (fold change, -2.04), miR-125b (fold change, -2.56), miR-21 (fold change, -2.22)) previously shown to modulate the expression of genes from pathways involved in lipoprotein metabolism pathways were successfully validated by qPCR.

CONCLUSIONS These findings provide evidence that microRNA can discriminate individuals with atherogenic dyslipidemia who are at risk for cardiovascular disease. Further research is need to determine if these same microRNA can distinguish other individuals with atherogenic dyslipidemia (e.g. women, other ethnic groups), and if these microRNA change in response to cardiovascular risk reduction interventions.