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

Biol Psychiatry. 2004 Sep 15;56(6):406-10. doi: 10.1016/j.biopsych.2004.06.020.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine / genetics
  • Cell Line, Tumor
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cysteine / genetics
  • Genes, Reporter / physiology
  • Glycine / genetics
  • Humans
  • Linkage Disequilibrium
  • Neuroblastoma
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / physiology*
  • Receptor, Serotonin, 5-HT2A / genetics*
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Threonine / genetics
  • Transfection / methods


  • Receptor, Serotonin, 5-HT2A
  • Threonine
  • Chloramphenicol O-Acetyltransferase
  • Cysteine
  • Alanine
  • Glycine