Abusive Inheritance; Gene Implicated in Alcoholism May Influence a Wide Array of Drug Abuse

By Bower, Bruce | Science News, November 14, 1992 | Go to article overview

Abusive Inheritance; Gene Implicated in Alcoholism May Influence a Wide Array of Drug Abuse


Bower, Bruce, Science News


Gene implicated in alcoholism may influence a wide array of drug abuse

Of the approximately 100,000 genes that make up humanity's chemical blueprint, the D2 dopamine receptor gene currently attracts by far the most controversy. For more than two years, scientists have wrangled over whether a particular form of the D2 gene confers a susceptibility to severe alcoholism.

The latest twist in this debate goes beyond the bottle. A research team directed by neuroscientist George R. Uhl of Johns Hopkins University School of Medicine in Baltimore now reports that a second version of the D2 dopamine receptor gene - called B1 - appears more often among people who indulge heavily in several addictive drugs, including alcohol, cigarettes, marijuana, cocaine, heroin, tranquilizers, and amphetamines.

Many such drug abusers consume several types of substances, and few abstain from alcohol, Uhl's group notes.

This second form of the D2 gene shows a moderate, statistically significant association with heavy use of several drugs, the scientists report in the September ARCHIVES OF GENERAL PSYCHIATRY. Still, the absence of a robust link leaves considerable room for social and psychological influences on alcoholism, cigarette dependence, and other drug abuse, they hold (SN: 2/1/92, p.69). It also suggests that additional genes help create a proclivity for substance abuse, the investigators note.

Proponents of the D2 dopamine receptor gene as a prominent player in severe alcoholism welcome its implication in a broader spectrum of drug abuse, while critics see significant flaws in the new study. Both camps anxiously await the findings of federal researchers currently employing advanced molecular scanning techniques to search for specific chemical changes in the D2 gene that may distinguish alcoholics from non-alcoholics.

Uhl and his associates collected blood samples from 232 drug users who met the criteria for moderate or heavy use of several drugs - usually including alcohol and cigarettes - and from 56 controls who either used no drugs or on rare occasions consumed alcohol, cigarettes, or marijuana. The researchers isolated DNA from each blood sample, used special enzymes to cut the DNA into fragments, and placed the pieces into an electrically charged gel that sorted them into identifiable patterns. The investigators then used chemical probes to mark specific amino acid variations along two stretches of the D2 gene.

Heavy users of several drugs displayed a substantial excess of the B1 form of the D2 gene - which features a chemical modification near an "active" region responsible for producing and regulating proteins of dopamine receptors on brain cells. Dopamine serves as a chemical messenger and has important effects on pleasure-seeking behaviors.

One-third of the multiple-drug users displayed the B1 variant, compared with 14 percent of the controls, Uhl's group asserts. Further analysis indicates that alcoholics did not skew these results: One-third of the drug users who were not heavy alcohol drinkers possessed the B1 variant.

However, the extent of the association between the B1 variant and the abuse of multiple substances falls far short of that reported between the D2 gene and alcoholism by Kenneth Blum, a psychopharmacologist at the University of Texas Health Science Center at San Antonio, and Ernest P. Noble, a psychiatrist at the University of California, Los Angeles (SN: 9/21/91, p.190).

Noble views the new data on multiple-drug abuse as supportive of his theory that the dopamine receptor gene is one of several genes that predispose people to a broad spectrum of substance use and abuse. As further evidence for this notion, Noble cites an unpublished study conducted with Blum of two D2 gene variations - the same ones studied by Uhl's group - which showed an excess of both forms among cocaine abusers who abstain from other drugs. …

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