Polesskaya Oxana O, Aston Christopher, Sokolov Boris P
Molecular Neurobiology Branch, National Institute on Drug Abuse, NIH, DHHS, Baltimore, Maryland 21224, USA.
J Neurosci Res. 2006 Feb 15;83(3):362-73. doi: 10.1002/jnr.20732.
Differential DNA methylation has been suggested to contribute to differential activity of alleles C and T and thereby to genetic associations between the C/T(102) polymorphism in the 5-HT2A receptor gene (5HT2AR) and psychiatric disorders. We surveyed methylation in two CpG sites, which are specific to allele C. The majority of allele C-specific CpG sites were methylated in human temporal cortex and peripheral leukocytes and levels of methylation varied between individuals. Levels of methylation in the promoter correlated significantly with the expression of 5HT2AR. Methylation of allele C-specific CpG sites in the first exon correlated significantly with the expression of DNA methylase 1 (DNMT1) but not S-adenosylhomocysteine hydrolase (AHCY). These findings support the hypothesis that allele-specific DNA methylation is involved in regulation of 5HT2AR expression, influencing expression differences between alleles C and T.
差异性DNA甲基化被认为有助于等位基因C和T的差异性活性，从而导致5-羟色胺2A受体基因（5HT2AR）中C/T(102)多态性与精神疾病之间的遗传关联。我们调查了两个仅对等位基因C特异的CpG位点的甲基化情况。大多数等位基因C特异的CpG位点在人类颞叶皮质和外周血白细胞中发生甲基化，且甲基化水平在个体间存在差异。启动子中的甲基化水平与5HT2AR的表达显著相关。第一外显子中等位基因C特异的CpG位点的甲基化与DNA甲基化酶1（DNMT1）的表达显著相关，但与S-腺苷同型半胱氨酸水解酶（AHCY）的表达无关。这些发现支持了这样的假说，即等位基因特异性DNA甲基化参与5HT2AR表达的调控，影响等位基因C和T之间的表达差异。
