Alcoholism: Gene may put you at greater risk

Written by PTI | Washington | Updated: Aug 28 2014, 21:52pm hrs
AlcoholismResearchers suspect that Nf1 gene might be relevant to alcohol-related activity in a specific area of the brain. (Thinkstock)
Scientists have identified a gene that plays a key role in the development of alcoholism and alcohol dependence.

Researchers at The Scripps Research Institute (TSRI) found that variations in a gene, called neurofibromatosis type 1 (Nf1) are linked to alcohol-dependence risk and severity in patients.

Researchers found that a specific signalling pathway associated with alcohol dependence is regulated by Nf1 - which was linked with excessive drinking in mice.

The study found that Nf1 regulates gamma-aminobutyric acid (GABA), a neurotransmitter that lowers anxiety and increases feelings of relaxation.

Researchers have long sought a gene or genes that might be responsible for risk and severity of alcohol dependence.

"Despite a significant genetic contribution to alcohol dependence, few risk genes have been identified to date, and their mechanisms of action are generally poorly understood," said TSRI Staff Scientist Vez Repunte-Canonigo, co-first author of the study.

While the new study showed that Nf1 is one of those rare risk genes, the researchers were not sure exactly how Nf1 affected the brain.

The team suspected that Nf1 might be relevant to alcohol-related GABA activity in an area of the brain called the central amygdala, which is important in decision-making and stress- and addiction-related processes.

"As GABA release in the central amygdala has been shown to be critical in the transition from recreational drinking to alcohol dependence, we thought that Nf1 regulation of GABA release might be relevant to alcohol consumption," said Herman.

The team tested several behavioural models, including a model in which mice escalate alcohol drinking after repeated withdrawal periods, to study the effects of partially deleting Nf1.

In this experiment, which simulated the transition to excessive drinking that is associated with alcohol dependence in humans, they found that mice with functional Nf1 genes steadily increased their ethanol intake starting after just one episode of withdrawal.

Conversely, mice with a partially deleted Nf1 gene showed no increase in alcohol consumption.

The researchers found that in mice with partially deleted Nf1 genes, alcohol consumption did not further increase GABA release in the central amygdala.

In contrast, in mice with functional Nf1 genes, alcohol consumption resulted in an increase in central amygdala GABA.

In the second part of the study, a collaboration with a distinguished group of geneticists at various US institutions, the team analysed data on human variations of the Nf1 gene from about 9,000 people.

The results showed an association between the gene and alcohol-dependence risk and severity.

The study is published in the journal Biological Psychiatry.