Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression

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. We have earlier...

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Bibliographic Details
Published in:Biological psychiatry (1969) 2004-06, Vol.55 (11), p.1090-1094
Main Authors: Hranilovic, Dubravka, Stefulj, Jasminka, Schwab, Sibylle, Borrmann-Hassenbach, Margitta, Albus, Margot, Jernej, Branimir, Wildenauer, Dieter
Format: Article
Language:English
Subjects:
5-HTTLPR
5-hydroxytryptamine
Adult
Adult and adolescent clinical studies
Analysis of Variance
Biological and medical sciences
Carrier Proteins - genetics
Carrier Proteins - metabolism
Family Health
Female
Gene Expression - physiology
Genotype
Humans
lymphoblasts
Lymphocytes - metabolism
Male
Medical sciences
Membrane Glycoproteins - genetics
Membrane Glycoproteins - metabolism
Membrane Transport Proteins
Minisatellite Repeats - genetics
mRNA
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Polymorphism, Genetic
Promoter Regions, Genetic
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Psychoses
real-time PCR
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Schizophrenia
Schizophrenia - genetics
Serotonin Plasma Membrane Transport Proteins
VNTR-2
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Summary: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. 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 β-actin as reference. 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 (∼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). Our results indicate weak individual influence, but possible combined effect, of 5-HTTLPR and VNTR-2 polymorphisms on 5-HTT gene expression.
ISSN:0006-3223
1873-2402
DOI:10.1016/j.biopsych.2004.01.029