Reduced expression of circadian clock genes in male alcoholic patients.
BACKGROUND
There are clear interactions between chronic alcohol consumption and circadian rhythmicity that is regulated by several circadian clock genes. The altered expressions of these genes have been mainly described in animals. The mammalian master clock in the suprachiasmatic nuclei orchestrates the biological rhythms in peripheral tissues. As peripheral blood mononuclear cells (PBMCs) are the most accessible tissue clinically, we assessed the mRNA levels of these genes in patients with alcohol dependence (AD) undergoing alcohol-withdrawal (AW) treatment.


METHODS
Twenty-two male patients fulfilled the DSM-IV diagnostic criteria of AD, and 12 comparison healthy control subjects were recruited. The patients with AD were further divided by the presence of delirium tremens (DTs), the most severe form of AW syndrome, into DT group and non-DT group. All the participants received blood withdrawal at 9 am, while the patients with AD had blood collection twice: on the next morning of admission (baseline) and on the seventh day. PBMCs were isolated from whole blood, and the mRNA expression profiles of hClock1, hBmal1, hPer1, hPer2, hCry1, and hCry2 were determined by quantitative real-time PCR.


RESULTS
The baseline mRNA levels of the target circadian clock genes were markedly lower in patients with AD than in control subjects. After 1 week of alcohol detoxification, there were very limited restorations of discrete circadian gene expressions. DT group did not differ in the expression patterns of circadian clock genes from non-DT group.


CONCLUSIONS
This is the first study demonstrating the overall lowering of circadian clock genes among patients with AD. The expression pattern is comparable between patients with and without DTs. Although preliminary with data at only one single time point, the observation of strikingly reduced mRNA levels supports the association between circadian clock gene dysregulation and chronic alcohol intake.
Huang
Ming-Chyi
MC
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ho
Chia-Wei
CW
Chen
Chun-Hsin
CH
Liu
Shing-Cheng
SC
Chen
Chiao-Chicy
CC
Leu
Sy-Jye
SJ
D000328:Adult; D000430:Alcohol Withdrawal Delirium / Q000235:genetics / Q000523:psychology; D000437:Alcoholism / Q000235:genetics*; D056926:CLOCK Proteins / Q000187:drug effects* / Q000235:genetics*; D002940:Circadian Rhythm / Q000187:drug effects* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013695:Temperance
D056926:CLOCK Proteins