An important genetic study conducted through Mayo Clinic has identified vital new information concerning alcoholism in subjects with European ancestry, according to a recent issue of Alcohol: Clinical and Experimental Research.
Research findings indicate that alcohol dependence is highly inheritable, although specific genes and their variations associated with this illness remain unknown. Animal model studies allow identification of potential candidate genes but their relevance to alcoholism in humans and its complications, including alcohol withdrawal and seizures, require additional research. Under the direction of Victor Karpyak, M.D., Ph.D., of the Mayo Clinic Department of Psychiatry and Psychology, a team of clinical and basic scientists investigated the sequence of the human MPDZ gene and its association with risks for alcohol dependence and alcohol withdrawal seizures.
"We have long known that the presence of severe withdrawal and seizures indicates strong physical dependence on alcohol," states Dr. Karpyak. "Focus on this group of subjects increases our chances to successfully identify the genetic variations associated with alcoholism in general and the presence of withdrawal symptoms specifically."
Sophisticated genetic research in mice isolated small regions on mouse chromosomes linked to severity of acute alcohol and barbiturate withdrawal measured by the presence and severity of seizures. Further research demonstrated that MPDZ gene is the only one in this chromosome region which has variants associated with severity of acute alcohol and barbiturate withdrawal and seizures.
The MPDZ protein is an important scaffolding brain protein, responsible for synaptic structure and plasticity. It is also known to be involved in learning and memory as well as seizures and epilepsy and, thus, is a good candidate for the human study focused on genetic predictors for alcohol withdrawal. Unfortunately, little was known about sequence variability of the MPDZ gene in humans. It is also a very long gene and its sequencing required considerable effort and costs.