"The shared heritability between smoking and alcoholism, particularly in heavy smokers and heavy drinkers, indicates that some genes predispose individuals to both smoking and drinking," said Mary-Anne Enoch, a staff scientist in the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism and corresponding author for the study. "Nicotine's effects on the brain occur mainly through nicotinic acetylcholine receptors, and alcohol acts on these same receptors to release dopamine, the 'pleasure' hormone in the brain's reward pathway."
Enoch added that the enzyme COMT plays an important role in the breakdown of dopamine and norepinephrine in the brain, its activity varying according to a common COMT polymorphism, Val158Met. "The Met allele results in a less efficient enzyme and therefore probably more dopamine and norepinephrine in the brain," she said. "The Met allele has also been associated with increased anxiety and neuroticism, increased emotionality in response to pain, and greater brain activation in response to unpleasant visual images."
Whereas studies of European men have shown that the Met allele is associated with late onset alcoholism and increased alcohol intake in social drinkers, Enoch and her colleagues have found that in American Indians the Met allele was protective against alcoholism, and the Val allele was the risk allele.
"The answer to this paradox may lie in the relationship between anxiety and drinking patterns," she said. "In societies where regular, daily drinking is the norm, such as in Europe, anxious Met individuals may be more vulnerable to alcoholism through using alcohol as a coping mechanism. In societies where heavy, periodic drinking bouts are the norm, such as in some American Indian tribes, anxious Met individuals may be less likely to participate in this kind of risky behavior and may be protected from alcoholism."
Enoch and her colleagues also found that the Val allele was a risk factor for smoking, but only in women.
For the current study, researchers recruited 342 (201 women, 141 men) community-based Plains American Indians, establishing their lifetime drinking and smoking histories. Additionally, five COMT loci – including Val158Met – were genotyped.
"There are three key findings," said Enoch. "One, Plains Indians have very different drinking patterns. Alcoholics drink heavily, but episodically … yet they still meet the criteria for alcoholism."
Two, she continued, "they have a very different comorbidity. They don't smoke heavily." In statistical terms, although 62 percent of the male alcoholics and 40 percent of the female alcoholics were smokers, only 12 percent of the alcoholic men and eight percent of the alcoholic women smoked heavily.
"And three," she noted, "at least one third are social smokers who never progress to 'real' smoking, they just smoke in social settings. This may be a throwback to the traditional use of tobacco amongst American Indians."
Enoch said that this study shows how there is no such thing as an "alcoholism gene" or "alcoholism allele."
"Here you've got one gene, and in one population one allele of the gene is associated with a disease, alcoholism, yet in another population, the gene's other allele is associated with that disease," she said. "You've really got to look at the gene-environment interaction when you've got a gene like this, with two common variants."
Furthermore, she said, researchers cannot extrapolate findings from one group to another. "The vast majority of alcoholism studies are conducted among male alcoholics, and also among treatment alcoholics. The assumption has always been 'everything you find in Caucasian men can be applied to everyone else,' but this study shows that you cannot."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Sex Differences in the Influence of COMT Val158Met on Alcoholism and Smoking in Plains American Indians," were: Juwaria F. Waheed, Claudia R. Harris, and David Goldman of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism; and Bernard Albaugh of the Center for Human Behavior Studies, Inc. of Weatherford, Oklahoma. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health, and the Office of Research on Minority Health.
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