This article is a US Government work and, as such, is in the public domain in the United States of America.
Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics†
Article first published online: 7 FEB 2002
Published 2002 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 67, Issue 6, pages 812–822, 15 March 2002
How to Cite
Polesskaya, O. O. and Sokolov, B. P. (2002), Differential expression of the “C” and “T” alleles of the 5-HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics. J. Neurosci. Res., 67: 812–822. doi: 10.1002/jnr.10173
- Issue published online: 28 FEB 2002
- Article first published online: 7 FEB 2002
- Manuscript Accepted: 11 DEC 2001
- Manuscript Revised: 10 DEC 2001
- Manuscript Received: 20 OCT 2001
- Stanley Foundation
- allele ratio;
- postmortem brain;
- 5-HT2A mRNA;
- 5-HT2A protein;
A genetic association between schizophrenia and a silent C/T(102) polymorphism in the 5-HT2A receptor gene (5-HT2AR) has been previously reported; however, the mechanisms underlying this association remain unknown. Here we developed an improved quantitative assay for measurements of allele ratios, which revealed that the expression of allele “C” in the temporal cortex of normal heterozygous individuals was significantly lower than the expression of allele “T” (allele “C” to allele “T” ratio of ∼0.8, P < 0.0001). Confirming decreased expression of allele “C,” total levels of 5-HT2AR mRNA and protein in normal individuals with the C/C genotype were lower than in individuals with the T/T genotype. Similarly to normal individuals, allele “C” to allele “T” ratio in heterozygous schizophrenics was reduced (∼0.8, P < 0001). This ratio was independent of neuroleptic treatment history. By contrast, total levels of 5-HT2AR mRNA correlated inversely with neuroleptic free interval prior to death (r = −0.67, P < 0.001) suggesting a reversible neuroleptic effect. Total levels 5-HT2AR mRNA in neuroleptic free (> 26 weeks) schizophrenics (n = 11) were significantly lower than in controls (P = 0.03). The data suggest that increased prevalence of allele “C” among schizophrenics may be due to intrinsically low expression of this allele, which may contribute to a deficit in 5-HT2AR expression in some schizophrenics. Published 2002 Wiley-Liss, Inc.