Background
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.
Methods
To investigate possible functional effects of –1438A/G on either promoter, two different
reporter gene assays were used in three cell lines.
Results
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.
Conclusions
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.
Keywords
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© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
