FINAL REPORT: microRNA Expression Profile in Migraine: the microMIG study

Summary

Migraine is a complex brain disorder and is the second most disabling neurologic condition overall. Multiple factors, including both genetic and environmental mechanisms seem to play a role in migraine, which has a polygenic heritability pattern. So far, 39 loci have been found to be related to common migraine. However, each of these genes has a relatively modest effect.

Environmental factors may modulate the expression of DNA. Therefore, epigenetics, the study of environmentally influenced genetic regulatory mechanisms, could further the understanding of migraine pathophysiology and provide insight into migraine chronification.

Among the epigenetic regulatory mechanisms, microRNAs (miRNA) act as key regulators of genetic expression by inhibiting transcription or promoting degradation of selected messenger RNAs (mRNAs). A single miRNA sequence could regulate multiple mRNAs and help mediate the environmentally induced changes in genetic expression. miRNAs have been found intracellularly and in all body fluids. Accessing the central nervous system is too invasive, so looking at peripheral blood mononuclear cells (PBMC) is an indirect measure of changes that might be going on in the brain. Their gene expression can reflect brain changes. For instance, differential miRNA expression profiles have been identified in chronic pain conditions, psychiatric conditions, and neurological disorders.

In this project, we found a characteristic miRNA profile for migraine. The next step will be to validate this in a larger, more heterogeneous international cohort.

Hypothesis vs. Findings

Our hypothesis is that changes in the miRNA expression profiles of PBMC may signal, and possibly mediate, the changes of the brain in migraine. Hence, the goal of our study was to find differentially expressed miRNAs in PBMC of episodic (EM) and chronic migraine (CM) patients compared to healthy controls.

We designed and performed an epigenetic case control study to compare the expression of miRNA in PBMC among patients with CM, EM and healthy controls using miRNA microarrays. We found a specific profile of miRNAs in migraine, specifically: 5 significant differentially expressed miRNAs between healthy controls and all migraineurs (CM+EM), 10 between controls and CM, and 8 between controls and EM. As a result, we found the results we expected.

Unanswered Questions

We will continue this study by replicating our results first in a local cohort and then in a larger, more heterogeneous international cohort. Our goal is to find a final microRNA signature for migraine.

What this Research Means to You

The Migraine Research Foundation and Association of Migraine Disorders grant has allowed us to complete the first steps in this migraine epigenetics project. We plan to continue working in this line of research to help us better understand the pathophysiology of migraine and someday, to have a translational impact on our patients.