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Mayo Clinic Study Finds Gene Bringing Together Animal and Human Research in Alcoholism
Date:4/23/2009

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.

To investigate the relevance of the model findings in animals for human alcoholism, Dr. Karpyak and his collaborators resequenced the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures, 59 subjects with a history of withdrawal without seizures and 64 samples from non-alcoholic subjects -- all with European American ancestry. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequencing allowed the first opportunity of comparing the MPDZ gene in humans and mice. The new Mayo study found that the human gene does not have variations identical to those comprising the MPDZ gene associated with alcohol withdrawal seizures in mice.

Second, researchers used common variants to compare haplotype structure of the MPDZ gene in alcohol dependent subjects with and without history of withdrawal seizures and in controls who did not have alcoholism. The study revealed a significant association between MPDZ gene variant alcohol-dependency without seizures, compared to the control subjects. Contrary to initial hypothesis and animal findings, the study showed no significant association between MPDZ sequence variants and withdrawal seizures in humans. This suggests the potential role of MPDZ in alcoholism and/or related phenotypes other than alcohol withdrawal seizures.

This important new information supports further investigation of the role of MPDZ gene in alcoholism
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SOURCE Mayo Clinic
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