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The –1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity

Parsons, Michael J. ; D'Souza, Ursula M. ; Arranz, Maria-Jesus ; Kerwin, Robert W. ; Makoff, Andrew J.

Biological psychiatry (1969), 2004-09, Vol.56 (6), p.406-410 [Periódico revisado por pares]

New York, NY: Elsevier Inc

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Título:
The –1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity
Autor: Parsons, Michael J. ; D'Souza, Ursula M. ; Arranz, Maria-Jesus ; Kerwin, Robert W. ; Makoff, Andrew J.
Assuntos: 1438A/G polymorphism ; 5-HT2A receptor ; Alanine - genetics ; Biochemistry and metabolism ; Biological and medical sciences ; Cell Line, Tumor ; Central nervous system ; Chloramphenicol O-Acetyltransferase - metabolism ; Cysteine - genetics ; enhancer ; Fundamental and applied biological sciences. Psychology ; Genes, Reporter - physiology ; Glycine - genetics ; Humans ; Linkage Disequilibrium ; Neuroblastoma ; Polymorphism, Single Nucleotide - genetics ; promoter ; Promoter Regions, Genetic - physiology ; psychiatric disorders ; Receptor, Serotonin, 5-HT2A - genetics ; Receptor, Serotonin, 5-HT2A - metabolism ; reporter gene assay ; Threonine - genetics ; Transfection - methods ; Vertebrates: nervous system and sense organs
É parte de: Biological psychiatry (1969), 2004-09, Vol.56 (6), p.406-410
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: The –1438A/G single nucleotide polymorphism (SNP) lies just upstream of two alternative promoters for the 5-hydroxytryptamine type 2A (5-HT2A) receptor gene (HTR2A) and is in strong linkage disequilibrium with the 102T/C SNP. Both SNPs are associated with numerous psychiatric disorders and related phenotypes. A possible functional affect of the –1438A/G SNP might underlie associations of both linked SNPs with these neuropsychiatric disorders. A prior investigation into affects of this SNP on promoter function, lacking the more downstream promoter, found no significant difference with a reporter gene assay. To investigate possible functional effects of –1438A/G on either promoter, two different reporter gene assays were used in three cell lines. Promoter activity was consistently detected that, in the presence of the SV40 enhancer, was significantly greater in the presence of the A allele relative to the G allele but only in cell lines that express endogenous HTR2A, suggesting that transcriptional factor(s) and the presence of both promoters might be necessary to elicit this effect. These findings show that the –1438A/G SNP has the potential to modulate HTR2A promoter activity and might be the functional variant responsible for the associations of both SNPs with many neuropsychiatric phenotypes.
Editor: New York, NY: Elsevier Inc
Idioma: Inglês

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The –1438A/G polymorphism in the 5-hydroxytryptamine type 2A receptor gene affects promoter activity

Parsons, Michael J. ; D'Souza, Ursula M. ; Arranz, Maria-Jesus ; Kerwin, Robert W. ; Makoff, Andrew J.

New York, NY: Elsevier Inc

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