Study Supports Genetic Link to Alcoholism : Medicine: Duarte City of Hope researchers say their findings confirm controversial earlier results. But they suspect that the gene is a ‘modifying’ one that, with other factors, increases risk.
California researchers say they have confirmed a controversial finding of a genetic factor in alcoholism, but they suspect the gene is not the cause but a “modifying” gene that conspires with other genetic and social factors to increase risk.
The finding, published today in the Journal of the American Medical Assn., is said to represent the first instance in which a series of independent studies have found that a specific gene may influence the development of a common behavioral disorder.
The gene, found in blood and tissue samples, appears to be more prevalent not only in alcoholics but also among people with Tourette’s syndrome, attention deficit hyperactivity disorder and autism, according to the researchers at City of Hope National Medical Center in Duarte.
“I think it’s a beginning of a whole new field of genetics and human behavior,” said Dr. David E. Comings, who headed the study. “The 20th Century was the century of Freud; the 21st Century is going to be the century of genes, as far as behavior is concerned.”
However, a study in the same issue of the journal by researchers at Yale University School of Medicine failed to find an association between the gene and alcoholism--a striking discrepancy that the researchers attributed to differences in methodology.
“The issue is not settled yet,” said Dr. Joel Gelernter, a co-author of the Yale study. “There have been interesting and provocative results presented. My negative study cannot disprove any positive study; it can only make us look at it very carefully.”
The alcoholism gene research follows an April, 1990, paper in which researchers at UCLA and the University of Texas reported that they had found that a certain form of a gene long believed to play a role in addictive behavior was especially common among severe alcoholics.
In that study, the researchers found the gene in 77% of samples of genetic material from severe alcoholics. It was absent from 72% of samples from non-alcoholics. They said the findings suggested that the gene left people susceptible to at least one form of alcoholism.
The study stirred intense interest within medicine and among the public. It seemed to lend credence to the notion that alcoholism is a disease and to raise the possibility of new approaches to alcoholism counseling, prevention and treatment.
Since that time, other research groups have reported on similar studies. Some have duplicated the original finding while others have not, triggering some sniping over methodology and calls for new approaches to the question.
“This is an extraordinary time for neurogenetics,” said James P. MacMurray, director of alcohol and drug treatment at the Jerry L. Pettis Memorial Veterans Hospital in Loma Linda. “Almost on a monthly basis, there is a new wrinkle that is emerging on this.”
“Most of the workers in the field would agree there are significant genetic and environmental factors involved,” said Dr. David Goldman of the U.S. National Institute on Alcohol Abuse and Alcoholism. “The problem now is to identify them.”
The gene being studied, known as the dopamine D2 receptor gene, helps structure the brain’s reward system and a person’s ability to experience pleasure. It comes in one of two versions, known as the A1 allele and the A2 allele. The A1 allele is the one under scrutiny.
In Comings’ study, he and other researchers in California, New York, Massachusetts and Georgia compared the frequency of the A1 allele in alcoholics and people with several behavior disorders to the frequency of the allele in a group of controls.
The researchers found the gene in 24.5% of the controls, and in 14.5% of the controls known not to be alcoholics. By contrast, they found it in 42.3% of the alcoholics they studied, 44.9% of people with Tourette’s syndrome, 46.2% of those with attention deficit hyperactivity disorder and 54.5% of those with autism.
“This is not the primary gene for any of these disorders,” said Comings, director of the Department of Medical Genetics at City of Hope. Comings believes it is a modifying gene that might, for example, exacerbate a condition already present.
“You can’t say that someone who has this gene is either going to have alcoholism or Tourette’s syndrome or any of these other conditions,” Comings said. “. . . If you found the other gene or genes (more directly involved), the possibility of predicting might increase. But right now, this is not a diagnostic test for any of these.”
In the same issue of the journal, the Yale researchers also examined the frequency of the gene in alcoholics and random controls. But they found no significant difference between the two groups.
Gelernter, an assistant professor of psychiatry, said the difference between the two studies’ findings might be attributable to methodological differences. For example, he said the two groups used different criteria for diagnosing alcoholism.
Furthermore, the frequency of the gene varies widely among racial, ethnic and ancestral groups.
If a study inadvertently included a large number of a particular group, the result could be distorted, perhaps suggesting an association where there is none, researchers say.
Both Gelernter and Goldman said any relationship between the gene and alcoholism will remain unproven until researchers identify a structural difference in the gene or a specific difference in the chemical processes in the brains of people with the gene.
But in an editorial accompanying the papers, Dr. C. Robert Cloninger, a prominent researcher in the field, concluded “it is most likely” that the A1 allele “modifies the expression of other genes that have a major and direct influence on susceptibility to alcoholism.”
