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Candidate Gene Approach: Case-Control Serotonin-Metabolizing Enzymes Association Studies A tryptophan hydroxylase TPH intron variant that affects A logical approach to understanding vulnerability to alcohol splicing is associated with reduced 5-HIAA and suicidality addiction is to look directly for variants in genes involved in impulsive alcoholics 86, Because of the complexity of causation of alco- Studies in rats suggest that activation of 5-HT1B recep- Chapter Molecular and Cellular Genetics of Alcohol Addiction tors in the NAC may be inhibitory on the behavioral effects transcriptionally significant promoter polymorphisms offer of elevated mesolimbic dopamine transmission 88 by promising tools for understanding the roles of DRD2 primarily modulating the activity of glutamatergic hip- and DAT in alcoholism. In a large sib-pair linkage analysis Opioid Receptors of Finnish alcoholic criminal offenders, significant evidence of linkage and association of antisocial alcoholism to Three endogenous opioid receptors, and are the HTR1B GC was found, and this was also observed in targets of the major opioid peptides -endorphin, enke- a Southwest American Indian tribe, suggesting that a locus phalins, and dynorphins, respectively. The rewarding prop- predisposing to antisocial alcoholism may be linked to erties of - and -receptor ligands are brought about by HTR1B at 6q However, the functional Cys23Ser polymor- plicate the opioid system, particularly the opioid receptor, phism does not appear to be associated with alcohol depen- in both initial sensitivity or response to alcohol, and in the dence Some studies have found lished studies on the role of 5-HT variants in alcoholics. Findings were also nega- A composed of combinations of at least 14 different subunits.

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