DRD4 dopamine receptor genotype and CSF monoamine metabolites in Finnish alcoholics and controls

Wiley - Tập 60 Số 3 - Trang 199-205 - 1995
Megan Adamson1, James L. Kennedy2, Artūras Petronis2, Michael Dean1, Matti Virkkunen3, Markku Linnoila4, David Goldman1
1Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, DICBR, Rockville, Maryland
2Clarke Institute of Psychiatry and University of Toronto, Toronto, Ontario, Canada
3Department of Psychiatry, University of Helsinki, Sapinlahdentie 1, Helsinki, Finland
4Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, DICBR, Rockville, Maryland

Tóm tắt

AbstractThe DRD4 dopamine receptor is thus far unique among neurotransmitter receptors in having a highly polymorphic gene structure that has been reported to produce altered receptor functioning. These allelic variations are caused by a 48‐bp segment in exon III of the coding region which may be repeated from 2–10 times. Varying the numbers of repeated segments changes the length, structure, and, possibly, the functional efficiency of the receptor, which makes this gene an intriguing candidate for variations in dopamine‐related behaviors, such as alcoholism and drug abuse. Thus far, these DRD4 alleles have been investigated for association with schizophrenia, bipolar disorder, Parkinson's disease, and chronic alcoholism, and all have been largely negative for a direct association.We evaluated the DRD4 genotype in 226 Finish adult males, 113 of whom were alcoholics, many of the early onset type with features of impulsivity and antisocial traits. Genotype frequencies were compared to 113 Finnish controls who were free of alcohol abuse, substance abuse, and major mental illness. In 70 alcoholics and 20 controls, we measured CSF homovanillic acid (HVA), the major metabolite of dopamine, and 5‐hydroxyindoleacetic acid (5‐HIAA). No association was found between a particular DRD4 dopamine receptor allele and alcoholism. CSF concentrations of the monoamine metabolites showed no significant difference among the DRD4 genotypes.This study of the DRD4 dopamine receptor in alcoholics is the first to be conducted in a clinically and ethnically homogeneous population and to relate the DRD4 genotype to CSF monoamine concentrations. The results indicate that there is no association of the DRD4 receptor with alcoholism. © 1995 Wiley‐Liss, Inc.

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Wiley

Tập 60 Số 3

199-205

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