FREQUENCY OF THE A1 A2 ALLELES OF THE D2 DOPAMINE-RECEPTOR (DRD2) GENE IN A BRITISH, CAUCASIAN CONTROL-GROUP SCREENED TO EXCLUDE ALCOHOLISMAND HEAVY DRINKING/

Recent reports of a genetic association between restriction fragment l ength Polymorphisms at the D2 dopamine receptor locus (DRD2) on chromo some 11q and alcoholism have suggested involvement of the D2 receptor protein in the aetiology of alcoholism, smoking and possibly other dis orders. These allelic association findings have been criticized on the basis of the possible confounding of ethnic with disease differences, between allele frequencies of subjects and controls, and the fact tha t some of the control groups were not screened to exclude alcoholism o r heavy drinking. We have observed the frequency of the A1 and A2 alle les in a population of 307 Caucasian British individuals screened for alcohol consumption of less than the UK Royal College of Psychiatrists ' recommended sensible drinking limits for males and females and who a lso failed to qualify for a diagnosis of alcoholism according to the R esearch Diagnostic Criteria (RDC). The frequency of the A1 allele was found to be 0.20, which is slightly higher than most of the other scre ened Caucasian control groups from Europe and the United States. The a llele and genotype frequencies in our sample are a resource for compar ison with samples of alcoholics from the United Kingdom which have bee n selected on the basis of British ancestry and for residence in Londo n. When we combined our new control data with that of the previous Cau casian control samples we found a significantly higher frequency of A1 A1 homozygotes among the unscreened than the screened controls, sugges ting that the DRD2 locus may be involved in drinking variation among t he general population.