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UI Study Reveals Value of Schizophrenia-Related Gene Variation
February 14, 2007University 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. An abstract of the article is available at http://www3.interscience.wiley.com/cgi-bin/abstract/114112711/ABSTRACT.
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.
The study was funded in part by the National Institutes of Health. Donald Black, M.D., UI professor of psychiatry, was a co-author, and other UI experts in psychiatry and neurosciences also contributed to the research.
HOPA stands for Human Opposite Paired Element (the last two letters in the abbreviation are taken from the first two letters in the word "Paired.")
A UI news release on previous HOPA research is available online at:
http://www.news-releases.uiowa.edu/2004/april/041204schizophrenia.html
University of Iowa
"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.
The study was funded in part by the National Institutes of Health. Donald Black, M.D., UI professor of psychiatry, was a co-author, and other UI experts in psychiatry and neurosciences also contributed to the research.
HOPA stands for Human Opposite Paired Element (the last two letters in the abbreviation are taken from the first two letters in the word "Paired.")
A UI news release on previous HOPA research is available online at:
http://www.news-releases.uiowa.edu/2004/april/041204schizophrenia.html
University of Iowa
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A specific genetic region that has been increasingly identified as the strongest genetic link to psoriasis has an even more significant role in the chronic skin disease than has been suspected, University of Utah medical researchers show in a new study.
Variation in prostate stem cell antigen gene raises bladder cancer risk
Researchers have pinpointed a specific gene variation that causes increased risk of urinary bladder cancer, according to a scientific team led by The University of Texas M. D. Anderson Cancer Center.
UMMS researchers isolate first 'neuroprotective' gene in patients with amyotrophic lateral sclerosis
A genetic variant that substantially improves survival of individuals with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.
Study reveals specific gene in adolescent men with delinquent peers
Birds of a feather flock together, according to the old adage, and adolescent males who possess a certain type of variation in a specific gene are more likely to flock to delinquent peers.
Genes may make some people more prone to anxiety
Inborn differences may help explain why trauma gives some people bad memories and others the nightmare of post-traumatic stress. Scientists in Germany and the United States have reported evidence linking genes to anxious behavior. The findings appear in the August issue of Behavioral Neuroscience, published by the American Psychological Association.
Mental stress reduces blood flow to the heart in patients with gene variation
University of Florida researchers have identified a gene variation in heart disease patients who appear especially vulnerable to the physical effects of mental stress - to the point where blood flow to the heart is greatly reduced.
Cigarette after Valentine snuggle deadlier for some
The proverbial cigarette after a Valentine's Day snuggle can prematurely end a love affair, as new evidence emerges that a common defect in a gene significantly increases a smoker's risk of an early heart attack.
Researchers challenge previous findings regarding widely used asthma treatment
A new study published recently in The Lancet reveals that one of the most commonly used asthma medicines -- long-acting beta-agonists -- may not be associated with adverse events in people based on their genotype (gene variation), as previous studies had shown.
Gene variation may elevate risk of liver tumor in patients with cirrhosis
A particular gene variation appears to significantly increase the risk that individuals with cirrhosis of the liver will go on to develop hepatocellular carcinoma (HCC), a liver tumor that is the third leading cause of cancer death.
First new multiple sclerosis gene found in 30 years
A newly identified gene may hold the promise of guiding future research into therapies for multiple sclerosis in what its discoverers say is the first major genetic advance in 30 years for understanding this nervous system disease.
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