PubMed · 4116631
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1972-10-28. Alcoholic hyperlipidaemia.. https://pubmed.ncbi.nlm.nih.gov/4116631/
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The human dopamine D2 receptor gene (DRD2) has received considerable attention for the past several years as a potential candidate that may affect susceptibility to alcoholism. The association studies that compared the frequencies of alleles of DRD2 gene between alcoholics and control groups have produced equivocal results. Dopamine D3 and D4 receptor genes (DRD3 and DRD4) are in the same class as DRD2 but with different pharmacological properties. We have used relative risk and haplotype relative risk approaches to test associations between alleles of DRD3 and DRD4 genes and alcoholism. For relative risk studies 162 probands from multiple incidence alcoholic families have been compared to 89 psychiatrically normal controls. Haplotype relative risk approaches have used 29 alcoholic probands in which both parents were available for genotyping. The Bal I restriction enzyme site in DRD3 and tandem repeat (VNTR) in DRD4 genes polymorphisms were used to genotype the above samples. The results of relative risk approaches for both DRD3 and DRD4 genes were negative for comparisons of alcoholics and subtypes of alcoholics with normal controls. Haplotype relative risk approaches also were negative for both genes. These results suggest that any role played by these receptors may account for only part of the variation in susceptibility to alcoholism.
We evaluated the involvement of tyrosine hydroxylase (TH) mutations in susceptibility to manic-depressive disease (MDD) and alcoholism (ALC) with a cladistics-based association analysis. Eighty-one probands with MDD, 113 probands with alcoholism, and 80 normal controls were tested for differences in frequency of nine haplotypes at the TH locus. The haplotypes were comprised of four restriction fragment length polymorphisms spanning the TH gene. A cladogram constructed from the haplotypes provided the evolutionary context for a nested statistical analysis. Statistically significant evidence was found for association of a subgroup of the sample for each of the disorders with different branches of the gene tree, but the findings were sensitive to minor changes in estimated haplotype frequencies.