Original Investigation

Human Genetics

, Volume 97, Issue 5, pp 614-619

First online:

Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: Identification of two naturally occurring receptor variants and association analysis in schizophrenia

  • Jeanette ErdmannAffiliated withInstitute of Human Genetics, University of Bonn
  • , Daphne Shimron-AbarbanellAffiliated withInstitute of Human Genetics, University of Bonn
  • , Marcella RietschelAffiliated withDepartment of Psychiatry, University of Bonn
  • , Margot AlbusAffiliated withState Mental Hospital Haar
  • , Wolfgang MaierAffiliated withDepartment of Psychiatry, University of Mainz
  • , Judith KörnerAffiliated withDepartment of Psychiatry, University of Bonn
  • , Brigitta BondyAffiliated withDepartment of Psychiatry, University of Munich
  • , Kevin ChenAffiliated withDepartment of Molecular Pharmacology and Toxicology, University of Southern California
  • , Jean C. ShihAffiliated withDepartment of Molecular Pharmacology and Toxicology, University of Southern California
    • , Michael KnappAffiliated withDepartment for Medical Statistics, University of Bonn
    • , Peter ProppingAffiliated withInstitute of Human Genetics, University of Bonn
    • , Markus M. NöthenAffiliated withInstitute of Human Genetics, University of Bonn Email author 

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Abstract

A statistically significant association between a silent mutation (102T/C) in the serotonin-2A (5-HT2A) receptor gene and schizophrenia has recently been reported in a sample of Japanese patients and healthy controls. This finding suggests that genetic predisposition to schizophrenia may be affected by a functional 5-HT2A receptor variant that is in linkage disequilibrium with 102T/C. In the present study, we have sought to identify genetic variation in the 5-HT2A receptor gene by screening genomic DNA samples from 91 unrelated subjects comprising 45 patients with schizophrenia and 46 healthy controls by using single-strand conformation analysis. We have identified four nucleotide sequence variants. Two sequence changes would result in protein alterations: a substitution of threonine by asparagine at position 25 (Thr25Asn), and a substitution of histidine by tyrosine at position 452 (His452Tyr). In order to test for a possible contribution to the development of schizophrenia, we have determined allele frequencies in extended samples of unrelated patients and healthy controls. The two amino acid substitutions are found with similar frequencies in patients and controls, indicating that the presence of these variants is not causally related to the development of schizophrenia. However, the reported association of the non-coding polymorphism 102T/C with the disease has also been detected in our sample (P = 0.041, odds ratio = 1.28, 95% confidence interval 1.012–1.623).