磯部 一郎

DNA methylation in gene promoter regions influences gene expression. Circadian clock genes play an important role in the formation of a biological clock and aberrant methylation of these genes contributes to several disorders. In this study, we examined forensic autopsy specimens to determine whether DNA methylation status in the promoter regions of nine circadian clock genes (Per1, Per2, Per3, Cry1, Cry2, Bmal1, Clock, Tim, and Ck1e) is related to a change in acquired diathesis and/or causes of death. Methylation-specific PCR and direct sequencing methods revealed that the promoters of Per1, Cry2, Bmal1, Clock, and Ck1e were unmethylated in all the forensic autopsy specimens, while the promoters of Per2, Per3, Cry1, and Tim were partially methylated. Methylation status varied between individuals and between tissues in the same patient. A detailed analysis of methylation patterns in the Cry1 promoter region revealed that the patterns also varied between individuals and the Cry1 promoter had highly methylated patterns in two cases that had been exposed to methamphetamine. These results suggest that the methylation status of clock gene promoters varies between individuals. Methamphetamine use may influence methylation in the Cry1 gene promoter region and disturb circadian rhythmicity. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Inherited mutations in the human cardiac sodium channel (SCN5A) gene cause arrhythmogenic diseases such as tachyarrhythmia and bradyarrhythmia. Moreover, mutation subsets in the coding region impair SCN5A function, potentially leading to sudden cardiac death (SCD). In the present study, we performed diplotype analysis of the regulatory region of the SCN5A gene in Japanese people who died suddenly because of an unknown cause (sudden death group n = 70) and controls (n = 112). There were no significant differences at six polymorphic loci between the groups. However, 38 diplotypes of 6-nucleotide polymorphism variants were identified. One of these diplotypes-Dip.D (CTG-TC/CCG-TC)-occurred significantly more frequently in the sudden death group than in the controls (p &lt 0.01, OR = 5.18, 95% CI: 1.38-19.45). Dip.D has two variants (T-1062C and T-847G), and while it is unclear whether these directly affect mRNA expression, a common polymorphism in this region modulates SCN5A expression in vitro. Our results thus suggest that the transcription of the SCN5A Dip.D variant may be associated with arrhythmogenic diseases that can induce sudden death. © 2009 Elsevier Ireland Ltd. All rights reserved.