title: Polymorphisms in the regulatory region of the human serotonin 5-HT2A receptor gene (HTR2A) influence gene expression.
abstract: BACKGROUND
  Genomic variation in the regulatory region of the serotonin (5-HT) 2A receptor gene (HTR2A) may contribute to altered levels of 5-HT2A receptor and to psychiatric disease.
  
  
  METHODS
  Frequency and linkage disequilibrium (LD) were determined for promoter single nucleotide polymorphisms (SNPs) -1438A/G, -1420C/T, and -783A/G in 156 subjects. Functional relevance of -1438A/G and -783A/G was assayed in vitro using a luciferase reporter assay and ex vivo using quantitative real time polymerase chain reaction in a set of human fibroblast cell lines.
  
  
  RESULTS
  Significant LD was observed between SNPs -1438A/G and -783A/G. In vitro assays showed no significant differences in promoter activity between the A- and G-allele of -1438 locus when expressed with the major alleles at -1420C/T and -783A/G; however, when the minor allele G at -783 was expressed with G-allele at -1438, promoter activity was significantly decreased. 5-HT2A receptor mRNA expression in human fibroblast cell lines confirmed that -783A/G polymorphism significantly modified the effects of -1438A/G SNP.
  
  
  CONCLUSIONS
  Our results demonstrate that SNP -783A/G modifies the effects of the major SNP -1438A/G. Future studies examining the association of -1438A/G polymorphism with diseases and 5-HT2A receptor expression analyses should account for this epistasis.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232-8548, USA.
authors.forename: Regina L
authors.initials: RL
authors.lastname: Myers
authors.forename: David C
authors.initials: DC
authors.lastname: Airey
authors.forename: D Hal
authors.initials: DH
authors.lastname: Manier
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.forename: Elaine
authors.initials: E
authors.lastname: Sanders-Bush
mesh_terms: D000328:Adult; D004843:Epistasis, Genetic; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A