AUTHOR=Strafella Claudia , Caputo Valerio , Termine Andrea , Assogna Francesca , Pellicano Clelia , Pontieri Francesco E. , Macchiusi Lucia , Minozzi Giulietta , Gambardella Stefano , Centonze Diego , Bossù Paola , Spalletta Gianfranco , Caltagirone Carlo , Giardina Emiliano , Cascella Raffaella 

TITLE=Immune System and Neuroinflammation in Idiopathic Parkinson’s Disease: Association Analysis of Genetic Variants and miRNAs Interactions

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.651971

DOI=10.3389/fgene.2021.651971

ISSN=1664-8021

ABSTRACT=<p>The present study investigated the association of SNPs involved in the regulation of immune response, cellular degenerative and neuroinflammatory pathways with the susceptibility and progression of idiopathic Parkinson’s Disease (PD). In particular, 342 PD patients were subjected to a genotyping analysis of a panel of 120 SNPs by Open Array Technology. As control group, 503 samples representative of the European general population were utilized. The genetic analysis identified 26 SNPs associated with PD susceptibility. Of them, 12 SNPs were described as significant expression Quantitative Loci (eQTL) variants in different brain regions associated with motor and non-motor PD phenomenology. Moreover, the study highlighted 11 novel susceptibility genes for PD, which may alter multiple signaling pathways critically involved in peripheral immune response, neuroinflammation, neurodegeneration and dopaminergic neurons wiring. The study of miRNA-target genes highlighted a possible role of miR-499a, miR-196a2, and miR-29a in the modulation of multiple neuroinflammatory and neurodegenerative mechanisms underlying PD physiopathology. The study described a network of interconnected genes (<italic>APOE</italic>, <italic>CLU</italic>, <italic>IL6</italic>, <italic>IL7R</italic>, <italic>IL12B</italic>, <italic>INPP5D</italic>, <italic>MAPK1</italic>, <italic>MEF2C</italic>, <italic>MIF</italic>, and <italic>TNFSF14</italic>), which may act as upstream regulators in the modulation of biological pathways relevant to PD. Intriguingly, <italic>IL6</italic> stands out as a master gene regulator since it may indirectly regulate the network of interconnected genes. The study highlighted different genes and miRNAs interactions potentially involved in PD physiopathology, which are worth to be further explored to improve the knowledge of disease and the research of novel treatments strategies.</p>