Study reveals value of schizophrenia-related gene variation

Feb 13, 2007

University of Iowa researchers have learned more about a genetic variation that is a small risk factor for a mild form of schizophrenia yet also is associated with improved overall survival.

The findings, which appear online in the American Journal of Medical Genetics, could help lead to treatments for schizophrenia and even other illnesses, and ways to leverage the gene variation's advantages.

This HOPA12pb gene variation advance drew on a genetic database that was about five times larger than sample sizes used in previous research, said Robert Philibert, M.D., Ph.D., associate professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine and the study's co-author.

"The study used the National Institute of Mental Health's largest publicly available sample, and thus it provides even more convincing evidence that the gene variation is worth studying," Philibert said.

The genetic variation causes a change in the portion of the protein that regulates the development of dopamine-releasing neurons. Antipsychotic drugs work by blocking dopamine, but drug treatments have limited success, and so scientists seek other ways to treat patients.

The team analyzed the genetic data of 900 European-Americans and found the HOPA gene variation in 22 individuals. Although the gene variation accounts for only an estimated .3 percent of all schizophrenia, nearly three of every 100 Caucasians have the gene variation.

"Most mutations associated with psychosis are found in only one in 10,000 or one in 100,000 individuals, and so these mutations do not lend themselves as study models," Philibert said. "HOPA is a relatively common mutation and that makes it valuable to study."

Philibert said that because HOPA often is a helpful gene variant, the fact that it sometimes is not reveals that it can react with environmental or other genetic factors to result in illness.

"If we can find a way to intervene in those interactions, then we may be able to avert disease and harness how this gene variation may help us," Philibert added.

In a current phase I, or safety, clinical trial, UI researchers are treating an individual who has a HOPA gene variation for symptoms of underactive thyroid.

"We don't know if this hypothyroidism is a direct effect of the gene or a genetic-environmental interaction," Philibert said. "We are using thyroid hormone supplementation to target the symptoms."

The UI Research Foundation and the National Institutes of Health (NIH) share a patent for HOPA12pb, which is found on the X-chromosome. Men are more likely than women to have this form of schizophrenia because it is X-linked. However, only about one in 30 men with the HOPA gene variation has schizophrenia.

An abstract of the article is available at www3.interscience.wiley.com/cg… t/114112711/ABSTRACT.

Source: University of Iowa

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