Linkage disequilibria at the D[sub 2] dopamine receptor locus (DRD2) in alcoholics and controls
- Washington Univ. School of Medicine, St. Louis, MO (United States)
Because of its central role in the neuromodulation of appetitive behaviors, the D[sub 2] dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to addictive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, the authors have assayed four DRD2 RFLPs that span coding regions as well as a 3[prime] flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism. 64 refs., 2 figs., 6 tabs.
- OSTI ID:
- 6588857
- Journal Information:
- Genomics; (United States), Vol. 19:1; ISSN 0888-7543
- Country of Publication:
- United States
- Language:
- English
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DOPAMINE
RECEPTORS
HUMAN CHROMOSOMES
GENETIC MAPPING
STATISTICS
AMINES
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHROMOSOMES
DRUGS
HYDROXY COMPOUNDS
MAPPING
MATHEMATICS
MEMBRANE PROTEINS
NEUROREGULATORS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
SYMPATHOMIMETICS
550400* - Genetics