Human Genetics

, Volume 97, Issue 5, pp 614–619

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

Authors

  • Jeanette Erdmann
    • Institute of Human GeneticsUniversity of Bonn
  • Daphne Shimron-Abarbanell
    • Institute of Human GeneticsUniversity of Bonn
  • Marcella Rietschel
    • Department of PsychiatryUniversity of Bonn
  • Margot Albus
    • State Mental Hospital Haar
  • Wolfgang Maier
    • Department of PsychiatryUniversity of Mainz
  • Judith Körner
    • Department of PsychiatryUniversity of Bonn
  • Brigitta Bondy
    • Department of PsychiatryUniversity of Munich
  • Kevin Chen
    • Department of Molecular Pharmacology and ToxicologyUniversity of Southern California
  • Jean C. Shih
    • Department of Molecular Pharmacology and ToxicologyUniversity of Southern California
  • Michael Knapp
    • Department for Medical StatisticsUniversity of Bonn
  • Peter Propping
    • Institute of Human GeneticsUniversity of Bonn
    • Institute of Human GeneticsUniversity of Bonn
Original Investigation

DOI: 10.1007/BF02281871

Cite this article as:
Erdmann, J., Shimron-Abarbanell, D., Rietschel, M. et al. Hum Genet (1996) 97: 614. doi:10.1007/BF02281871

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).

Copyright information

© Springer-Verlag 1996