A normal genetic variation modulates synaptic MMP‐9 protein levels and the severity of schizophrenia symptoms

• DOI: 10.15252/emmm.201707723
• Publication Date: 2017-06-17T00:10:13Z
• Authors: Katarzyna Lepeta; Katarzyna J Purzycka; Katarzyna Pachuls...; Marina Mitjans; Martin Begemann; Behnam Vafadari; Krystian Bijata; Ryszard W Adamiak; Hannelore Ehrenreich; Magdalena Dziembo...; Leszek Kaczmarek
• Keywords: SNP; Genetic Association

Abstract Matrix metalloproteinase 9 ( MMP ‐9) has recently emerged as a molecule that contributes to pathological synaptic plasticity in schizophrenia, but explanation of the underlying mechanisms been missing. In present study, we performed phenotype‐based genetic association study PGAS ) > 1,000 schizophrenia patients from Göttingen Research Association for Schizophrenia GRAS data collection and found an between ‐9 rs20544 C/T single‐nucleotide polymorphism SNP located 3′untranslated region UTR severity chronic delusional syndrome. cultured neurons, influenced activity morphology dendritic spines. We demonstrated Fragile X mental retardation protein FMRP bound 3′ . also dramatic changes RNA structure folding alterations affinity , depending on variant. Finally, observed greater sensitivity psychosis‐related locomotor hyperactivity Mmp heterozygous mice. propose novel mechanism involves ‐9‐dependent spine pathophysiology providing first mechanistic insights into way which single base change gene (rs20544) influences function results phenotypic patients.