Family-based study of markers at the 5′-flanking region of the human dopamine transporter gene reveals potential association with schizophrenic psychoses

  • Gerald Stöber
  • Julia Sprandel
  • Burkhard Jabs
  • Bruno Pfuhlmann
  • Kerstin Möller-Ehrlich
  • Michael Knapp
ORIGINAL PAPER
First Online:
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Accepted:

Abstract

The dopamine hypothesis of schizophrenia proposes an inherited or acquired presynaptic hyperactivity of dopaminergic neurons. The human dopamine transporter gene (hSLC6A3; hDAT) represents one major mechanism for the termination of dopaminergic neurotransmission. This study examines the degree of genetic association of the 5′-untranslated region (5′-UTR) of the hSLC6A3 to schizophrenia in a family-based association design. Five single nucleotide polymorphisms (SNPs) derived by a previous systematic mutation scan ∼1.2 kb of the 5′-UTR of the hSLC6A3 locus were genotyped for transmission disequilibrium between 82 index cases (56 males) with schizophrenia and their biological parents. We observed no preferential transmission of alleles from heterozygous parents to affected offspring. Five estimated haplotypes accounted for a frequency of 90% in the index cases, and were identical in cases and non-transmitted parental control haplotypes. Distinct five-locus-genotypes accumulated in schizophrenia compared to parental controls at P-value 0.0038 with odds-ratio of 2.02 (95% CI 0.99–4.14). In conclusion, our present findings support the genetic involvement of distinct hSLC6A3 genotypes in schizophrenia. We propose replication in extended samples and examination of the functional relevance of the associated genotypes on human dopamine transporter expression.

Key words

dopamine transporter hSLC6A3 gene promoter polymorphism schizophrenia 
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Copyright information

© Steinkopff Verlag Darmstadt 2006

Authors and Affiliations

  • Gerald Stöber
    • 1
  • Julia Sprandel
    • 1
  • Burkhard Jabs
    • 1
  • Bruno Pfuhlmann
    • 1
  • Kerstin Möller-Ehrlich
    • 1
  • Michael Knapp
    • 2
  1. 1.Department of Psychiatry and PsychotherapyUniversity of WürzburgWürzburgGermany
  2. 2.Institute of Medical Biometry, Informatics and EpidemiologyUniversity of BonnBonnGermany

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