Gene in the Bottle: A Controversial Alcoholism Gene Gets a New Twist

Article excerpt

Research into the genetics of alcoholism invariably stirs up spirited controversy. A report issued last year, describing the first evidence that a specific gene creates a susceptibility to at least one type of alcoholism, proved no exception. Critics immediately pointed out flaws in the study, and independent follow-up investigations suggested that the gene plays no role in fostering uncontrollable alcohol consumption.

But the gene will not go away. Its original proponents -- who had identified the culprit as one of two genes that occupy a precise spot on chromosome 11 and direct the function of key dopamine receptors on brain cells -- now report further evidence linking it to cases of severe alcoholism with medical complications. And another research group suggests that the gene may intensify the severity and medical consequences of alcoholism -- rather than cause the disorder -- by disturbing normal dopamine transmission. Dopamine, an important chemical messenger in the brain, normally helps to regulate pleasure-seeking behaviors.

"We may have found a gene that modifies, rather than causes alcoholism," says psychiatrist Ernest P. Noble of the University of California, Los Angeles, who co-directed the original study with psychopharmacologist Kenneth Blum of the University of Texas Health Science Center at San Antonio. "We just don't know yet. As research continues, I think we'll find many genes associated with alcoholism."

For now, though, the dopamine receptor gene stands alone. Noble's team first reported finding it in DNA from 24 of 35 alcoholics, compared with only seven of 35 nonalcoholics. All DNA samples came from the brain tissue of deceased individuals. The researchers used medical records and reports from family members to determine which individuals met the criteria for alcoholism. Because most of the alcoholics had failed in several rehabilitation efforts and had died of alcohol-related causes, the investigators concluded they had suffered from a severe form of the disorder (SN: 4/21/90, p.246).

Another study, reported last January, raised doubts about the proposed alcoholism gene. These researchers, led by psychiatrist Annabel M. Bolos of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Md., examined DNA from 40 alcoholics and 127 nonalcoholic controls, including 62 with cystic fibrosis. In both groups, the dopamine receptor gene turned up in about one-third of the volunteers. Bolos and her colleagues contended that psychiatric interviews with the participants, all of whom were living, allowed for more accurate alcoholism diagnoses than those deduced by Noble's group (SN: 1/12/91, p.29).

But Noble and Blum, who have re-examined data from the Bolos study, say the results actually support a link between the dopamine receptor gene and severe alcoholism. According to their analysis, the gene's prevalence increased from 25 percent of the nonalcoholic controls (excluding those with cystic fibrosis, who often die before alcoholism has a chance to develop, according to Noble and Blum) to 30 percent of the 20 alcoholics with no medical complications and 45 percent of the 20 alcoholics with related medical conditions such as liver cirrhosis. Bolos' group excluded alcoholics with the most severe, "acutely active" medical complications, thereby lowering the frequency of the dopamine receptor gene in their study, Noble and Blum maintain in the May 22/29 JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION.

In a commentary accompanying Noble and Blum's argument, Bolos and her colleagues question the revision of their work, noting that a standard alcoholism screening test reveals no difference in symptom severity between alcoholic participants with and without the gene.

Noble and his colleagues continue to pursue the chromosome 11 offender. …