Promoter specific methylation of the dopamine transporter gene is altered in alcohol dependence and associated with craving

Alcohol dependence is increasingly becoming a social issue. Mesolimbic dopaminergic pathway is responsible for the positive reward that leads to reinforcing action thus causing dependence. In- patient detoxification treatment is now very common. However, the treatment is not easy, due to the withdrawal symptoms and constant alcohol cravings. Epigenetic regulation of alpha- synuclein promoter region via DNA methylation affects dopaminergic neurotransmission, which is involved in alcohol dependence. This reduces the expression of alpha- synuclein which led to lowered alcohol craving. This finding inspired Hillemacher and his group to study the regulation of other genes involved in the dopaminergic neurotransmission in patients with alcohol dependence.

Dopamine transporter (DAT) plays a crucial role in the reuptake of dopamine from synaptic gap to stimulate the mesolimbic dopaminergic reward pathway. The study performed by Hillemacher and his group evaluated the difference in DAT promoter methylation between patients with alcohol dependence and healthy controls. They also established a possible association with alcohol craving.  Promoter specific DNA methylation status of total leukocyte DNA was measured using a methylation specific endonuclease digestion followed by real time PCR. Findings suggest that the DAT promoter is significantly hypermethylated in alcohol dependent patients. Decrease expression of DAT due to hypermethylation of the promoter would lead to elevated levels of dopamine in the synaptic gap. This might be associated with the decrease in alcohol craving.

During the detoxification treatment, abstinence of alcohol was required and this would cause a decrease in DNA methylation, thus leading to alcohol cravings. Alcohol consumption would then lead to the suppression of withdrawal craving.

Alcohol is bad. But we all still love it.

Loh Mun Jo-anne

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