Steven D. Flanagan

The dopamine D2 receptor gene: a genetic risk factor in substance abuse

Drug abuse has grown to epidemic proportions. Dopaminergic reward pathways have frequently been implicated in the etiology of drug addiction. To examine the possible role of genetic variants of the dopamine D2 (DRD2) gene in susceptibility to drug abuse we determined the prevalence of the TaqI A1 variant of the DRD2 gene in 200 white patients hospitalized in the Addiction Treatment Unit of a Veterans Administration Hospital. While the prevalence of the D2A1 allele was not significantly increased over controls, it did increase from 21% in subjects with alcohol abuse only to 32% in subjects with alcohol dependence only, consistent with other studies showing an association with the severity of alcoholism. By contrast, of 104 subjects with a discharge diagnosis of drug and alcohol abuse/dependence, 42.3% carried the D2A1 allele versus 29.0% of the 763 white controls (representing all white controls published to date) (P = 0.006). Of those who spent more than

Toroidal coil countercurrent chromatography in the affinity partitioning of nicotinic cholinergic receptor enriched membranes

25/week on two or more substances, 56.9% carried the D2A1 allele versus 28.2% of those abusing a single substance (P < 0.0005). Multiple logistic regression analysis showed a highly significant association between multiple substance abuse based on money spent and the presence of the D2A1 allele (P = 0.0003) and age of onset of abuse (P < 0.0001). D2A1 carriers exceeded D2A2A2 subjects for a history of being expelled from school for fighting (P = 0.001), and of those ever jailed for violent crimes, 53.1% carried the D2A1 allele versus 28.8% of those jailed for non-violent crimes (P = 0.011).(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein E genotype in patients with alzheimer's disease: Implications for the risk of dementia among relatives

Abstract A variation on the aqueous polymer phase partition method, affinity partitioning, has proved suitable for the preparative scale purification of binding site enriched membrane fragments. The full resolving potential of the affinity partitioning technique often requires the utilization of multiple extraction procedures such as countercurrent distribution. In this report, we evaluate the combination of a newly developed countercurrent purification technique, toroidal coil chromatography, with affinity partitioning. This approach provides an efficient method for purification and characterization of membrane bound nicotinic cholinergic receptors. The relative merits of the toroidal coil chromatography technology and the more conventional thin-layer countercurrent distribution techniques are compared.