DNA甲基化
血清素转运体
表观遗传学
双相情感障碍
单卵双胞胎
甲基化
表观基因组
遗传学
生物
狂躁
基因型
拷贝数变化
基因
心理学
心情
基因表达
精神科
基因组
作者
Hiroko Sugawara,Kazuya Iwamoto,Miki Bundo,Junko Ueda,Terukatsu Miyauchi,Atsuko Komori,An‐a Kazuno,Naoki Adati,Ichiro Kusumi,Yuji Okazaki,Jun Ishigooka,Takashi Kojima,Takeshi Kato
摘要
Bipolar disorder (BD) is a severe mental disorder characterized by recurrent episodes of mania and depression. Serotonin transporter (HTT) is a target of antidepressants and is one of the strongest candidate molecules of mood disorder, however, genetic study showed equivocal results. Here, we performed promoter-wide DNA methylation analysis of lymphoblastoid cell lines (LCLs) derived from two pairs of monozygotic twins discordant for BD. To rule out the possible discordance of copy number variation (CNV) between twins, we performed CNV analysis and found the copy number profiles were nearly identical between the twin pairs except for immunoglobulin-related regions. Among the three genes we obtained as candidate regions showing distinct difference of DNA methylation between one of the two pairs, hypermethylation of SLC6A4, encoding HTT, in the bipolar twin was only confirmed by bisulfite sequencing. Then, promoter hypermethylation of SLC6A4 in LCLs of BD patients was confirmed in a case-control analysis. DNA methylation of SLC6A4 was significantly correlated with its mRNA expression level in individuals with the S/S genotype of HTTLPR, and mRNA expression level was lower in BD patients carrying the S/S genotype. Finally, DNA methylation of the same site was also higher in the postmortem brains of BD patients. This is the first study to report the role of epigenetic modification of SLC6A4 in BD using an unbiased approach, which provides an insight for its pathophysiology.
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