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Surprises Found In Gene Variation Associated With Schizophrenia

Date:
April 12, 2004
Source:
University Of Iowa
Summary:
Approximately 2 percent of Caucasians have a gene segment variation that can cause a certain form of schizophrenia. Most people with the variation, known as a polymorphism, do not have the disease. A University of Iowa Health Care study reveals a good prognosis for people who do have this form of schizophrenia.

Approximately 2 percent of Caucasians have a gene segment variation that can cause a certain form of schizophrenia. Most people with the variation, known as a polymorphism, do not have the disease. A University of Iowa Health Care study reveals a good prognosis for people who do have this form of schizophrenia. The team also found that this polymorphism is associated with overall benefits for human survival, and the initial mutation occurred in a single common ancestor about 100,000 years ago.

The findings have implications for finding better ways to treat this particular type of schizophrenia and possibly augmenting the positive influences of the polymorphism on human survival. The findings also point the way for studying other gene defects. The UI Research Foundation and the National Institutes of Health (NIH) share a patent for this X-chromosome gene polymorphism, known as HOPA12pb. The study results appeared in the February 11 online issue of the American Journal of Medical Genetics.

"While this polymorphism makes us more vulnerable to a certain illness, in this case schizophrenia, overall it is evolutionarily beneficial," said Robert Philibert, M.D., Ph.D., UI associate professor of psychiatry in the Roy J. and Lucille A. Carver College of Medicine and the study's principal investigator.

"Traditionally, genes that are selected for human evolution affect two things -- resistance to infection and infant survival. This gene may be involved in both of these positive features," Philibert added.

While nearly one in 50 people of European extraction has the HOPA polymorphism, only a small minority of people with the variant gene sequence actually have schizophrenia. About one in 30 men with the particular polymorphism has the condition. Men are more likely than women to have this form of schizophrenia because the gene is X-chromosome linked.

People with HOPA-linked schizophrenia may have hallucinations. However, they do not have the "negative" symptoms found with most other forms of schizophrenia, such as compromised thinking, decreased attention and loss of emotion.

"We knew the gene causes a specific form of schizophrenia, but we didn't know that the type was associated with a good prognosis and marked by absence of negative symptoms," Philibert said. "Most individuals with this positive symptom schizophrenia are able to function in society and hold down jobs."

He added that the gene cannot by itself cause schizophrenia but must interact with other genes and environmental factors to result in illness. In addition to sometimes leading to schizophrenia, it also can cause hypothyroidism or obesity.

"It is critical to understand those interactions. If we can modulate them, we may be able to block the ill effects of this gene and keep the beneficial aspects," Philibert said.

HOPA stands for Human Opposite Paired Element. It was first isolated in 1994, when Philibert worked at the NIH.

"There are at least 25 genes in the gene complex in which HOPA participates. Several of the genes are known to be involved with other forms of human illness. Because this polymorphism is relatively common and because we have human models of it, it can be used as a paradigm to understand those other gene defects," Philibert added.

The type of evolutionary advantage -- resistance to disease -- that the UI team saw in the HOPA polymorphism also can be seen in a polymorphism linked to sickle cell anemia. In that condition, one copy of the polymorphism causes mild cell abnormalities but also provides resistance to malaria and thus promotes human survival. However, two copies of the variant gene cause the debilitating disease sickle cell anemia.

###

In addition to Philibert's contributions, the UI study included work by Nancy C. Andreasen, M.D., Ph.D., the Andrew H. Woods Chair of Psychiatry at the UI. Raymond Crowe, M.D., the George Winokur Professor of Psychiatry at the UI, also provided assistance with the investigation.

Funding for the study included a grant from the Nellie Ball Trust for Schizophrenia Research, a grant from the National Alliance for Research on Schizophrenia and Depression and several grants from the National Institute of Mental Health (part of the NIH).

The abstract for the study is available online at http://www3.interscience.wiley.com/cgi-bin/abstract/107614465/ABSTRACT

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.


Story Source:

The above story is based on materials provided by University Of Iowa. Note: Materials may be edited for content and length.


Cite This Page:

University Of Iowa. "Surprises Found In Gene Variation Associated With Schizophrenia." ScienceDaily. ScienceDaily, 12 April 2004. <www.sciencedaily.com/releases/2004/04/040412012037.htm>.
University Of Iowa. (2004, April 12). Surprises Found In Gene Variation Associated With Schizophrenia. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2004/04/040412012037.htm
University Of Iowa. "Surprises Found In Gene Variation Associated With Schizophrenia." ScienceDaily. www.sciencedaily.com/releases/2004/04/040412012037.htm (accessed July 25, 2014).

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