Title of article :
Serotonin transporter promoter and intron 2 polymorphisms: relationship between allelic variants and gene expression
Author/Authors :
Dubravka Hranilovic، نويسنده , , Jasminka Stefulj، نويسنده , , Sibylle Schwab، نويسنده , , Margitta Borrmann-Hassenbach، نويسنده , , Margot Albus، نويسنده , , Branimir Jernej، نويسنده , , Dieter Wildenauer، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
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 geneʹs 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 β-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 ( 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.
Keywords :
mRNA , real-time PCR , lymphoblasts , Schizophrenia , VNTR-2 , 5-hydroxytryptamine , 5-HTTLPR
Journal title :
Biological Psychiatry
Journal title :
Biological Psychiatry