Dysregulation of heart and brain specific micro-RNA in sudden infant death syndrome

Channelopathic heart arrhythmias and dysfunctional autonomic regulation of respiration and arousal based on defects in the brainstem are assumed to be involved in the pathogenesis of SIDS. There is evidence that, apart from mutational alterations in associated genes, disruption of physiological processes and deficient responses to external stressors may be influenced by the dysregulation of organ specific micro-RNA expression. It is unknown, however, whether these small, non-coding regulatory RNA molecules are involved in any SIDS pathomechanism. In a case-control study of two series of fresh-frozen heart tissue (n=14) and formalin fixed, paraffin embedded brainstem tissue (n=11) from SIDS and respective control cases, differential expression of heart and brain specific miR-1/miR-133 and miR-124a/let-7b, respectively, was determined using quantitative PCR analysis. Our results show a significant upregulation of heart specific miR-1 and brainspecific let-7b in SIDS compared to control cases. This pilot study is first to analyze differential miRNA expression in SIDS. Our findings suggest that organ specific miRNA dysregulation may be associated with SIDS pathogenesis and establishes the feasibility of miRNA analysis in different kinds of preserved and archived SIDS tissues.