title: Correlation between serotonin uptake in human blood platelets with the 44-bp polymorphism and the 17-bp variable number of tandem repeat of the serotonin transporter.
abstract: Dysfunctions of the central serotonin (5-hydroxytryptamine, 5-HT) system seem to be associated with psychiatric disorders such as schizophrenia or depression. Previous studies suggested that a 44-bp insertion/deletion polymorphism of the 5-HT transporter (5-HTT) promoter region might influence the transcriptional activity of the 5-HTT gene, and the insertion variant resulted in increased 5-HTT expression and 5-HT uptake. Moreover, a 17-bp variable number of tandem repeat (VNTR) polymorphism of the second intron may act as a transcriptional regulator with allele dependent differential enhancer-like properties. Since the 5-HTT of human platelets shares many properties with the transporter of neural tissue, platelets are widely used as a surrogate tissue source, possibly reflecting central 5-HT metabolism. Therefore, we investigated the impact of the 44-bp polymorphism and the 17-bp VNTR for 5-HT uptake in platelets of 50 male subjects. We found no significant effect of the 44-bp polymorphism and of the 17-bp VNTR on maximum rate (Vmax) of 5-HT uptake. However, individuals homozygous for the 5-HTT intron 2 allele with 12 repeats (STin2.12) of the 17-bp VNTR appeared to have lower affinity of 5-HT uptake than individuals heterozygous for the STin2.10/STin2.9 allele. This was also observed for the combined analysis of both polymorphisms. In conclusion, we found no association between the different genotypes of the 44-bp polymorphism and the 17-bp VNTR and maximum rate of 5-HT uptake into platelets.
authors.affiliation: Institute of Clinical Pharmacology, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany. rolf.kaiser@med.uni.gottingen.de
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaiser
authors.forename: Bruno
authors.initials: B
authors.lastname: Müller-Oerlinghausen
authors.forename: Diana
authors.initials: D
authors.lastname: Filler
authors.forename: Pierre-Benoit
authors.initials: PB
authors.lastname: Tremblay
authors.forename: Anne
authors.initials: A
authors.lastname: Berghöfer
authors.forename: Ivar
authors.initials: I
authors.lastname: Roots
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brockmöller
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001792:Blood Platelets / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins; D011110:Polymorphism, Genetic; D012701:Serotonin / Q000493:pharmacokinetics*; D050486:Serotonin Plasma Membrane Transport Proteins; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA