MicroRNAs as a marker of cardiovascular disease in Marfan syndrome and Marfan-related disorders

Abstract

Genetic counseling is an important process in the care of patients with Marfan syndrome and related disorders (MSRD) because it provides individualized risk assessment that can aid in determining prognosis and help healthcare specialists optimize management. Marfan syndrome affects many body systems, but aortopathy, or disease of the aorta, is the most common cause of death. Currently, resources for predicting the prognosis for cardiovascular complications in Marfan syndrome are limited. However, in several human diseases, microRNAs (miRNAs) have emerged as a promising biomarker, or quantifiable molecule in the body that can indicate the presence of disease (Ikonomidis et al., 2013; Khoury and Tran, 2015). Furthermore, miRNA profiles in peripheral blood are shown to be unique in aortic aneurysms of different etiologies possibly providing information regarding pathogenesis (Ikonomidis et al., 2013). This study explores the use of miRNAs as biomarkers in predicting onset and severity of aortopathy for patients with MSRD. The main hypothesis is that circulating miRNAs are unique in individuals with MSRD as compared to controls. A secondary aim is to determine whether unique miRNA profiles will aid in distinguishing between patients affected with Marfan syndrome that have high risk for aortic aneurysm from those with low risk for aortic aneurysm. Therefore, information gained from analyzing circulating miRNAs can provide personalized information about risk for aortopathy to aid in the genetic counseling process. In this study, the circulating miRNA profiles of 9 patients affected with MSRD were compared to unaffected controls using microarray expression profiling and statistical analysis. The results identified two significant circulating miRNAs that were up-regulated and twenty-nine that were down-regulated in patients with MSRD. Furthermore, results from cluster analysis and random forest plots showed that miRNA profiles can be used to distinguish between patients with MSRD and controls. In conclusion, the results from this project provide preliminary evidence that the circulating miRNA profiles are distinct between samples from patients affected with MSRD and those from unaffected controls. This data provides further evidence for the utility of miRNAs as a biomarker that can provide diagnostic information within the genetic counseling process.