MicroRNAs (miRNAs), a conserved class of small non-coding RNAs, serve as key post-transcriptional regulators of gene expression. MiRNAs have already been implicated in many human diseases through regulating diverse biological processes. Given the broad clinical and therapeutic potentials of miRNAs, it is of interest to know whether miRNAs may play a role in age-related disorders. Genetic variations in miRNA genes or in their binding sites within gene 3’UTRs are expected to affect miRNA function and substantially contribute to disease risk. In this thesis, the association of miRNA-related genetic variants with cardiovascular, neurodegenerative and ophthalmic disorders was systematically investigated followed by various in silico and in vitro validation studies. We found a number of miRNAs that are significantly associated with age-related disorders and can modify gene expression profiles in these complex disorders. Moreover, we showed that genetic variants in miRNAs and miRNA-binding sites could constitute part of the functional variants involved in these age-related disorders. These findings contribute to improve our understanding of the pathophysiology of cardiovascular, neurodegenerative and ophthalmic disorders.

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Keywords Age-related disorders, microRNAs, GWAS, Genetic variants
Promotor O.H. Franco (Oscar) , A. Dehghan (Abbas) , S.J. Erkeland (Stefan) , M.A. Meester-Smoor (Magda)
Publisher Erasmus University Rotterdam
Sponsor The research was supported by a scholarship from the Ministry of Health and Medical Education in IRAN and Mashhad University of Medical Sciences (MUMS), and by Utzchit grant awarded to M. Meester-Smoor.
ISBN 978-94-92863-49-6
Persistent URL hdl.handle.net/1765/100424
Ghanbari, M. (2017, July 5). The Role of MicroRNAs in Age-Related Disorders : From population-based genetic studies to experimental validation. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/100424