In the brain, histamine regulates a wide variety of physiological processes, including water and food intake, sleep-wake cycles, endocrine homeostasis, locomotion, and memory and learning. In a new study, researchers have found that decreased levels of brain histamine, which are associated with a functional polymorphism of histamine N-methyltransferase (HNMT) called Thr105 allele, may also result in higher levels of anxiety which may, in turn, confer vulnerability to alcoholism. Results are published in the March issue of Alcoholism: Clinical & Experimental Research.

"We were interested in examining the role of the functional Thr105Ile variant of HNMT because this is the enzyme which accounts for the degradation of histamine in mammalian brain," said Gabor Oroszi, a researcher at the National Institute on Alcohol Abuse and Alcoholism and first author of the study. "Since clinical experience with antihistamine drugs has indicated that blockade of histamine 1 receptors results in sedation, anxiolysis and sleepiness which are very strong in many patients we hypothesized that altered function of the sole histamine metabolizing enzyme in the brain might alter anxiety, a state frequently encountered by alcoholics."

Oroszi and his colleagues examined two distinct populations of alcoholics 218 Finnish Caucasians (206 males, 12 females) and 186 Plains American Indians (98 males, 88 females) for an association among the Thr105lle polymorphism, alcoholism, and "harm avoidance," a dimensional measure of anxious personality. Researchers also examined two groups of nonalcoholic "controls," 313 Finns (220 males, 93 females) and 140 Plains Indians (36 males, 104 females) for comparison's sake.

"We chose these two populations because they were well characterized in terms of both alcohol abuse and dependence, as well as harm avoidance," said Oroszi. "There was a sufficient number of alcoholics and nonalcoholic controls to allow us to compare
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14-Mar-2005

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