Multiple tissue methylation analysis of HTR2A exon I in suicidal behavior

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Abstract

Objective

The main aim of the current study was to investigate epigenetic alterations in serotonin 2A receptor (HTR2A) exon I CpG sites as possible risk factors for suicidal behavior. We also aimed to analyze the epigenetic alterations in two different tissues as epigenetic mechanisms are tissue specific. These epigenetic changes may lead to a better prediction of suicidal behavior.

Methods

Direct CpG methylation analysis was carried out on genomic DNA from the saliva of 20 schizophrenia suicide attempters and 27 non-attempters, and from post-mortem brain tissues of nine suicide victims and 11 controls. We used bisulfite pyrosequencing to assess the contributions of six CpG sites including the rs6313 (C102T) site in the first exon of HTR2A in suicide attempters and suicide victims.

Results

DNA methylation analysis did not find a significant difference in CpG methylation between suicide attempters and non-attempters (P=0.759) or between suicide victims and controls (P=0.189). We found a strong positive correlation between CpG methylation levels in blood and saliva (r=0.547, P<0.001).

Discussion

DNA methylation analysis confirmed that the overall methylation level of HTR2A exon I was around 80% for DNA extracted from saliva and almost 30% in the frontal cortex DNA. The results of this investigation do not support the evidence that methylation analysis of the HTR2A may be useful for investigating the epigenetic factors involved in suicidal behavior.

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