"Healthy people who carry a particular variant of the dopamine transporter gene, the nine repeat allele, have significantly higher levels of dopamine transporter in the brain," said the lead author, Christopher van Dyck, M.D., associate professor of psychiatry and neurobiology and director of the Alzheimer's Disease Research Unit and the Cognitive Disorders Clinic in the Department of Psychiatry.

The new study included 96 healthy European Americans--54 men and 42 women--who underwent a clinical examination to exclude any neurological or psychiatric disease, alcohol abuse or substance abuse. The levels of dopamine transporter availability were measured using SPECT imaging, and the dopamine transporter genotypes were determined by co-author Joel Gelernter, M.D.

"We are not yet sure if the effects of the variant on transporter levels in our healthy subjects can be generalized to neuropsychiatric disorders," van Dyck said. "If they can be, our results may be relevant for substance abuse, tobacco smoking, and ADHD. "The results suggest that the mechanism of association of this gene with several disorders could be altered levels of central dopamine transporter protein, influencing concentrations of extracellular dopamine."

This study replicated and expanded on a preliminary report by Leslie Jacobsen, M.D., and colleagues at Yale, although other studies of the effects of this variation on the availability of the dopamine transporter have yielded contradictory results.

In addition to Jacobsen and Gelernter, co-authors included Robert Malison, M.D., John Seibyl, M.D., Julie Staley, Marc Laruelle, M.D., Ronald Baldwin, and Robert Innis, M.D. The study was supported by grants and funds from the American Federation for Aging Research; Rose and Philip Hoffer; the Department of Veterans Affairs; the National Institute of Mental Health, and the National Institute on Drug Abuse.

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Because other factors, such as a population's migratory history, could influence genetic diversity in a general way, the authors also compared HLA diversity with the general genetic diversity expected for the population's location (this research group previously showed close correlation between diversity and location along ancient colonization routes).

The authors found that although human colonization history accounted for a certain degree of HLA diversity (as it does for other genes as well), the "local" richness of pathogen diversity also correlated significantly with the HLA diversity exhibited by individual populations, supporting the PDBS hypothesis. High HLA diversity tended to correlate with high pathogen diversity. In addition, the authors found that this correlation was especially strong for a particular type of HLA gene, HLA B. This finding is in agreement with past immunological and genetic studies showing that not all HLA class I proteins play identical roles and suggesting that pathogens--notably, viruses--may exert stronger evolutionary pressure on HLA B than on other HLA genes.

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