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Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50204

Hoehe,  Margret R.
Genetic Variation, Haplotypes, and Genetics of Complex Disease (Margret Hoehe), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Zitation

Patkar, A. A., Berrettini, W. H., Mannelli, P., Gopalakrishnan, R., Hoehe, M. R., Bilal, L., et al. (2004). Relationship between serotonin transporter gene polymorphisms and platelet serotonin transporter sites among African-American cocaine-dependent individuals and healthy volunteers. Psychiatric Genetics, 14(1), 25-32.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0010-88C5-4
Zusammenfassung
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.