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

Journal Article


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 ��-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.

Publication Date


  • 2004

Citation


  • Hranilovic, D., Stefulj, J., Schwab, S., Borrmann-Hassenbach, M., Albus, M., Jernej, B., & Wildenauer, D. (2004). Serotonin transporter promoter and intron 2 polymorphisms: Relationship between allelic variants and gene expression. Biological Psychiatry, 55(11), 1090-1094. doi:10.1016/j.biopsych.2004.01.029

Scopus Eid


  • 2-s2.0-2542447453

Web Of Science Accession Number


Start Page


  • 1090

End Page


  • 1094

Volume


  • 55

Issue


  • 11

Place Of Publication


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 ��-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.

Publication Date


  • 2004

Citation


  • Hranilovic, D., Stefulj, J., Schwab, S., Borrmann-Hassenbach, M., Albus, M., Jernej, B., & Wildenauer, D. (2004). Serotonin transporter promoter and intron 2 polymorphisms: Relationship between allelic variants and gene expression. Biological Psychiatry, 55(11), 1090-1094. doi:10.1016/j.biopsych.2004.01.029

Scopus Eid


  • 2-s2.0-2542447453

Web Of Science Accession Number


Start Page


  • 1090

End Page


  • 1094

Volume


  • 55

Issue


  • 11

Place Of Publication