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Family-based association study of the serotonin-2A receptor gene (5-HT2A) and bipolar disorder

The serotonin 2A receptor gene (5-HT2A) is of great interest for research in neuropsychiatric disorders based on the observation that various neuroleptic agents and antidepressants bind with relatively high affinity at 5-HT2A receptors, and the fact that the receptor density in platelets tends to in...

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Published in:Neuromolecular medicine 2002-01, Vol.2 (3), p.251-259
Main Authors: Ni, Xingqun, Trakalo, Joseph M, Mundo, Emanuela, Lee, Lisa, Parikh, Sagar, Kennedy, James L
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Trakalo, Joseph M
Mundo, Emanuela
Lee, Lisa
Parikh, Sagar
Kennedy, James L
description The serotonin 2A receptor gene (5-HT2A) is of great interest for research in neuropsychiatric disorders based on the observation that various neuroleptic agents and antidepressants bind with relatively high affinity at 5-HT2A receptors, and the fact that the receptor density in platelets tends to increase in depression. To test for the presence of association between 5-HT2A and bipolar disorder (BP), we studied a large number of triad families having probands affected with DSM-IV bipolar I (BPI), bipolar II (BPII) or schizoaffective disorder, bipolar type. Two polymorphisms of 5-HT2A, 102T/C, and His452Tyr were analyzed in the 274 bipolar triad families. Both the transmission disequilibrium test (TDT) and haplotype TDT were performed on the genotype data. We also calculated the maternal transmission and paternal transmission for each allele and compared the mean ages of onset across probands grouped by genotype at each of the two markers. No significant transmission disequilibrium between the alleles of 5-HT2A and BP was found. Separate studies of the sub-phenotypes also failed to demonstrate significant association. However, we found a trend towards transmission disequilibrium with the haplotype 102C.His452 (p = 0.0504). This trend may become more significant with a larger sample size. At present, results of this study suggest that the 5-HT2A is unlikely to play a major role in the genetic susceptibility to BP. Future studies will be directed towards increasing sample size, focusing on subtypes of BP or biochemical measures as phenotypes, and investigating other polymorphisms of 5-HT2A to provide more information at the DNA level.
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1559-1174
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subjects Adult
Age of Onset
Alleles
Amino Acid Sequence - genetics
Antidepressants
Bipolar disorder
Bipolar Disorder - genetics
Bipolar Disorder - metabolism
Brain Chemistry - genetics
DNA Mutational Analysis
DNA nucleotidylexotransferase
Female
Gene Frequency - genetics
Genetic Markers - genetics
Genetic Predisposition to Disease - genetics
Genetics
Genotype
Haplotypes
Haplotypes - genetics
Humans
Linkage Disequilibrium - genetics
Male
Mental disorders
Mutation - genetics
Phenotypes
Polymorphism, Genetic - genetics
Receptor density
Receptor, Serotonin, 5-HT2A
Receptors, Serotonin - genetics
Serotonin S2 receptors
title Family-based association study of the serotonin-2A receptor gene (5-HT2A) and bipolar disorder
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