title: Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression.
abstract: BACKGROUND
  Two polymorphic regions of serotonin transporter (5-HTT) gene: a 44 base pair (bp) insertion/deletion in the promoter region (5-HTTLPR) and a 17 bp variable number of tandem repeats in second intron (VNTR-2), seem to modulate the gene's transcription in allele-dependent manner.
  
  
  METHODS
  We have earlier demonstrated association with 5-HTT gene in families multiply affected by schizophrenia. Here, we investigated separate and combined effects of VNTR-2 and 5-HTTLPR on the rate of peripheral 5-HTT transcription in a sample of offspring from those families. Relative 5-HTT mRNA levels were determined in 53 permanent lymphoblast cell lines by semiquantitative real-time polymerase chain reaction using beta-actin as reference.
  
  
  RESULTS
  Since the low-expressing alleles (short [S], 10) appeared to act dominantly, genotypes were grouped as "high-expressing" (long [L]/L, 12/12) versus "low-expressing" (S, 10). At both loci, nonsignificant differences in 5-HTT mRNA levels ( approximately 30%) were observed between "high"- and "low-expressing" genotypes. In order to search for the potential combined effect of 5-HTTLPR and VNTR-2, levels of 5-HTT mRNA were compared among three groups of samples having "low-expressing" genotype at none, one, or both loci. Increase in number of "low-expressing" genotypes significantly reduced relative 5-HTT gene expression (p <.02).
  
  
  CONCLUSIONS
  Our results indicate weak individual influence, but possible combined effect, of 5-HTTLPR and VNTR-2 polymorphisms on 5-HTT gene expression.
authors.affiliation: Laboratory of Neurochemistry and Molecular Neurobiology, Department of Molecular Genetics, Rudjer Boskovic Institute, Zagreb, Croatia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Hranilovic
authors.forename: Jasminka
authors.initials: J
authors.lastname: Stefulj
authors.forename: Sibylle
authors.initials: S
authors.lastname: Schwab
authors.forename: Margitta
authors.initials: M
authors.lastname: Borrmann-Hassenbach
authors.forename: Margot
authors.initials: M
authors.lastname: Albus
authors.forename: Branimir
authors.initials: B
authors.lastname: Jernej
authors.forename: Dieter
authors.initials: D
authors.lastname: Wildenauer
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D018598:Minisatellite Repeats / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins