Background
The serotonin 2A receptor has been suggested to play a role in a number of mental diseases including obsessive-compulsive, schizophrenia, affective disorders, Tourette's syndrome and migraine. To evaluate the genetic influence on the phenotypical expression of the 5-HT2A receptor binding in the human brain in vivo, we examined the allelic variations of single nucleotide polymorphism G-1438A and T102C and measured [18F]altanserin binding in the brain with PET.
Methods
Sixty-eight controls were investigated with PET-[18F]altanserin using a bolus-infusion schedule to obtain steady-state of tracer in blood and tissue. Binding potential data for [18F]altanserin were measured in frontal cortex. A standard PCR procedure was used for genotyping. The comparison between groups was done by ANOVA, with age as a covariate.
Results
The allelic frequencies in our sample were: G-1438A g/g: 41%, g/a: 47% and a/a: 11%. T102C t/t: 42%, t/c: 47% and c/c: 11%. 5-HT2A receptor binding did not differ significantly between subjects within the three genotypes for each polymorphism (mean ± SD): G-1438A: g/g (n = 28): 2.31 ± 0.96, g/a (n = 32): 2.61± 0.80, a/a (n = 8): 2.60 ± 1.31. T102C: t/t (n = 29): 2.36 ± 0.99, t/c (n = 32): 2.61 ± 0.80, c/c (n = 7): 2.41 ± 1.28.
Conclusion
This study does not support the assumption that the genotypes G-1438A and T102C contribute directly to the regulation of the 5-HT2A receptors in the living human brain. That is, previous associations observed in obsessive-compulsive disorder and psychosis can not be substantiated through the phenotypic expression of 5-HT2A receptor binding.