Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers.
Alterations in the serotonin transporter (5-HTT) have been implicated in a variety of psychiatric disorders including cocaine dependence. A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) appears to influence the expression of 5-HTT in human cell lines. We investigated whether 5-HTTLPR variants were related to differences in measures of platelet 5-HTT sites in cocaine-dependent patients and healthy volunteers (controls). Polymerase chain reaction-based genotyping of a 44 base pair insertion/deletion polymorphism in 5-HTTLPR was performed in 138 cocaine-dependent African-American subjects and 60 African-American controls. This yielded a short (S) and a long (L) allele. Platelet 5-HTT sites were measured using the tritiated paroxetine binding assay. Relationships of 5-HTTLPR genotypes with Bmax (density of serotonin transporter) and Kd (affinity constant) were examined. Bmax values were significantly lower in cocaine-dependent patients (640 +/- 233) than controls (906 +/- 225) (P < 0.001); however, 5-HTTLPR genotype distributions or allele frequencies did not differ between the two groups. There were no significant differences in Bmax between the three genotypes among cocaine-dependent patients (LL = 690 +/- 246, LS = 620 +/- 235, SS = 587 +/- 183; P = 0.14) or controls (LL = 909 +/- 233, LS = 938 +/- 279, SS = 866 +/- 143; P = 0.65). All three genotypes in cocaine-dependent patients showed comparable reductions in Bmax from the corresponding genotypes in controls. Demographic variables, severity of substance use or depression were unrelated to Bmax or 5-HTTLPR genotypes. Although platelet 5-HTT densities are reduced in patients with cocaine dependence compared with healthy volunteers, these genotypic variations in the serotonin transporter do not seem to influence levels of platelet 5-HTT in cocaine-dependent patients or healthy volunteers.
Patkar
Ashwin A
AA
Department of Psychiatry and Human Behavior, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. ashwin.patkar@jefferson.edu
Berrettini
Wade H
WH
Mannelli
Paolo
P
Gopalakrishnan
Raman
R
Hoehe
Margret R
MR
Bilal
Louai
L
Weinstein
Stephen
S
Vergare
Michael J
MJ
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D017374:Paroxetine / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D017374:Paroxetine