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Neurogenetics

Previous studies investigating an association between alcoholism and the DRD2 variants Taq Al and 311Cys yielded conflicting results. Using DNA sequencing and PCR we typed four intragenic DRD2 sequence variants (intron 4 [398C..409A/398T.. 409G]; intron 6 [G2312CA/GA]; exon 7 311Ser -> Cys; exon 8 [1412A/G]) and the TaqI A RFLP downstream of DRD2 from 325 non-related Caucasian alcoholics diagnosed according to ICD-10. The patients investigated were recruited independently in three different institutions. 143 ethnically matched subjects without neuropsychiatric disorders served as controls. Based on the combined five-marker data we delineated 12 distinct DRD2 haplotypes and constructed a phylogenetic tree. Four haplotypes had frequencies of <0.01, and up to over 99% of the investigated chromosomes had one of the 8 more frequent haplotypes. We found a weak association of alcoholism to the [398T..409G]-allele of the intron 4 marker (p = 0.044). The increased frequency of this allele in the alcoholics was observed in all three clinical samples and almost exclusively due to increased frequencies of homozygotes. No significant association of alcoholism was observed to the Taq Al-allele, nor to the 311Cys variant. In all three clinical cohorts there was an increased frequency (14.8%, 13.3%, 9.7%; mean 12.2%) of a homozygous exon 8 1412G substitution compared to the controls (5.7%; p = 0.053). According to the proposed DRD2 phylogeny the exon 8 1412G-containing halotypes descend from an intron 4 [398T..409G]-bearing haplotype. Exon 8 1412G was almost exclusively linked with Taq A2. Our data might contradict the positive Taq Al-findings previously reported although an association of alcoholism to genetic variants of DRD2 cannot be excluded.



Headings
dopamine D2 receptor gene (DRD2)
alcoholism

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