Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?
Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5'-HTTLPR) among healthy control subjects but not alcohol-dependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5'-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p<0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of Bmax for paroxetine binding, but not Vmax for serotonin (5-HT) uptake, was lower than that for SS subjects (p<0.05). More L-carriers than their SS counterparts had Vmax for 5-HT uptake below 200 nmol/10(7) platelets-min (p<0.05) and Bmax for paroxetine binding below 600 nmol/mg protein (p<0.06). Current drinking (drinks per day during the past 14 days) correlated positively with Km and Vmax of platelet 5-HT uptake (p<0.05) and negatively with Bmax, but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with Km and Vmax of platelet 5-HT uptake (p<0.05) and B(max), but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.
Johnson
Bankole A
BA
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
Javors
Martin A
MA
Roache
John D
JD
Seneviratne
Chamindi
C
Bergeson
Susan E
SE
Ait-Daoud
Nassima
N
Dawes
Michael A
MA
Ma
Jennie Z
JZ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000097:blood* / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012189:Retrospective Studies; D012701:Serotonin / Q000097:blood*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D013223:Statistics as Topic
D017374:Paroxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors