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Alcoholism and Genetics

Research has shown conclusively that familial transmission of alcoholism risk is at least in part genetic and not just the result of family environment.Family-transmission-of-the-risk-for-alcoholism-is-partly-related-to-genetics.jpg

The task of current science is to identify what a person inherits that increases vulnerability to alcoholism and how inherited factors interact with the environment to cause disease. This information will provide the basis for identifying people at risk and for developing behavioral and pharmacologic approaches to prevent and treat alcohol problems.

The advances being made now are built on the discovery 50 years ago of the role in inheritance of DNA, the genetic material in cells that serves as a blueprint for the proteins that direct life processes. Alcoholism research, like other fields, is capitalizing on the scientific spinoffs of this milestone, among them the Human Genome Project and related efforts to sequence the genomes, the complete DNA sequences, of selected animals.

A Complex Genetic Disease

Studies in recent years have confirmed that identical twins, who share the same genes, are about twice as likely as fraternal twins, who share on average 50 percent of their genes, to resemble each other in terms of the presence of alcoholism. Recent research also reports that 50 to 60 percent of the risk for alcoholism is genetically determined, for both men and women. Genes alone do not preordain that someone will be alcoholic; features in the environment along with gene-environment interactions account for the remainder of the risk.

Research suggests that many genes play a role in shaping alcoholism risk.

Like diabetes and heart disease, alcoholism is considered genetically complex, distinguishing it from genetic diseases, such as cystic fibrosis, that result primarily from the action of one or two copies of a single gene and in which the environment plays a much smaller role, if any. The methods used to search for genes in complex diseases have to account for the fact that the effects of any one gene may be subtle and a different array of genes underlies risk in different people.

Scientists have bred lines of mice and rats that manifest specific and separate alcohol-related traits or phenotypes, such as sensitivity to alcohol’s intoxicating and sedative effects, the development of tolerance, the susceptibility to withdrawal symptoms, and alcohol-related organ damage. Risk for alcoholism in humans reflects the mix and magnitude of these and other phenotypes, shaped by underlying genes, in interaction with an environment in which alcohol is available. Genetic research on alcoholism seeks to tease apart the genetic underpinnings of these phenotypes and how they contribute to risk.

One well-characterized relationship between genes and alcoholism is the result of variation in the liver enzymes that metabolize (break down) alcohol. By speeding up the metabolism of alcohol to a toxic intermediate, acetaldehyde, or slowing down the conversion of acetaldehyde to acetate, genetic variants in the enzymes alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH) raise the level of acetaldehyde after drinking, causing symptoms that include flushing, nausea, and rapid heartbeat.

The genes for these enzymes and the alleles, or gene variants, that alter alcohol metabolism have been identified. Genes associated with flushing are more common among Asian populations than other ethnic groups, and the rates of drinking and alcoholism are correspondingly lower among Asian populations.

Genes, Behavior, and the Brain

Addiction is based in the brain. It involves memory, motivation, and emotional state. The processes involved in these aspects of brain function have thus been logical targets for the search for genes that underlie risk for alcoholism. Much of the information on potential alcohol-related genes has come from research on animals. Research has demonstrated a similarity in the mechanisms of many brain functions across species as well as an overlap between the genomes of animals—even invertebrates—and humans.

One approach to identifying alcohol-related genes is to start with an aspect of brain chemistry on which alcohol is thought to have an impact, and work forward, identifying and manipulating the underlying genes and ultimately determining whether the presence or absence of different forms of a gene influence alcoholism risk.

For example, genetic technology now permits scientists to delete or inactivate specific genes, or alternatively, to increase the expression of specific genes, and watch the effects in living animals. Because genes act in the context of many other genes, interpretation of these studies can be difficult. If one gene is disabled, for example, others may compensate for the loss of function. Alternatively, the loss of a single gene throughout development may be harmful or lethal. Nonetheless, these techniques can provide important clues to function. These approaches have been used to study how altering the expression of genes encoding the receptors(or their subunits) for neurotransmitters and intracellular messenger molecules alters the response to alcohol.

Genetic Studies in Humans

Knowledge gained from animal studies has assisted scientists in identifying the genes underlying brain chemistry in humans. Much research suggests that genes affecting the activity of the neurotransmitters serotonin and GABA (gamma-aminobutyric acid) are likely candidates for involvement in alcoholism risk. A recent preliminary study looked at five genes related to these two neurotransmitters in a group of men who had been followed over a 15-year period.

The men who had particular variants of genes for a serotonin transporter and for one type of GABA receptor showed lower response to alcohol at age 20 and were more likely to have met the criteria for alcoholism. Another study found that college students with a particular variant of the serotonin transporter gene consumed more alcohol per occasion, more often drank expressly to become inebriated, and engaged more frequently in binge drinking than students with another variant of the gene. The relationships between neurotransmitter genes and alcoholism are complex, however; not all studies have shown a connection between alcoholism risk and these genes.

Conclusions

Even from the first drink, individuals differ substantially in their response to alcohol. Genetics research is helping us understand how genes shape the metabolic and behavioral response to alcohol and what makes one person more vulnerable to addiction than another. An understanding of the genetic underpinnings of alcoholism can help us identify those at risk and, in the long term, provide the foundation for tailoring prevention and treatment according to the particular physiology of each individual.

 Learn more About Alcoholism and Other Drugs of Abuse

 

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