Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia

Erika Pedrosa, Karen A. Nolan, Radu Stefanescu, Pnina Hershcovitz, Tomas Novak, Ilja Zukov, Pavla Stopkova, Herbert M. Lachman

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background/Aims: Neuregulin 1 (NRG1) is a positional candidate gene in schizophrenia (SZ). Two major susceptibility loci in the NRG1 gene approximately one million nucleotides apart have been identified in genetic studies. Several candidate functional allelic variants have been described that might be involved in disease susceptibility. However, the findings are still preliminary. We recently mapped active promoters and other regulatory domains in several SZ and bipolar disorder (BD) candidate genes using ChIP-chip (chromatin immunoprecipitation hybridized to microarrays). One was the promoter for the NRG1 isoform, SMDF, which maps to the 3′ end of the gene complex. Analysis of the SNP database revealed several polymorphisms within the approximate borders of the region immunoprecipitated in our ChIP-chip experiments, one of which is rs7825588. Methods: This SNP was analyzed in patients with SZ and BD and its effect on promoter function was assessed by electromobility gel shift assays and luciferase reporter constructs. Results: A significant increase in homozygosity for the minor allele was found in patients with SZ (genotype distribution χ2 = 7.32, p = 0.03) but not in BD (genotype distribution χ2 = 0.52, p = 0.77). Molecular studies demonstrated modest, but statistically significant allele-specific differences in protein binding and promoter function. Conclusion: The findings suggest that homozygosity for rs725588 could be a risk genotype for SZ.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalNeuropsychobiology
Volume59
Issue number4
DOIs
StatePublished - Aug 2009

Fingerprint

Neuregulin-1
Schizophrenia
Protein Isoforms
Bipolar Disorder
Genotype
Genes
Single Nucleotide Polymorphism
Alleles
Chromatin Immunoprecipitation
Disease Susceptibility
Luciferases
Protein Binding
Nucleotides
Gels
Databases

Keywords

  • Bipolar disorder
  • Neuregulin
  • NRG1
  • rs725588
  • Schizophrenia
  • SMDF

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Neuropsychology and Physiological Psychology
  • Biological Psychiatry

Cite this

Pedrosa, E., Nolan, K. A., Stefanescu, R., Hershcovitz, P., Novak, T., Zukov, I., ... Lachman, H. M. (2009). Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia. Neuropsychobiology, 59(4), 205-212. https://doi.org/10.1159/000223732

Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia. / Pedrosa, Erika; Nolan, Karen A.; Stefanescu, Radu; Hershcovitz, Pnina; Novak, Tomas; Zukov, Ilja; Stopkova, Pavla; Lachman, Herbert M.

In: Neuropsychobiology, Vol. 59, No. 4, 08.2009, p. 205-212.

Research output: Contribution to journalArticle

Pedrosa, E, Nolan, KA, Stefanescu, R, Hershcovitz, P, Novak, T, Zukov, I, Stopkova, P & Lachman, HM 2009, 'Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia', Neuropsychobiology, vol. 59, no. 4, pp. 205-212. https://doi.org/10.1159/000223732
Pedrosa E, Nolan KA, Stefanescu R, Hershcovitz P, Novak T, Zukov I et al. Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia. Neuropsychobiology. 2009 Aug;59(4):205-212. https://doi.org/10.1159/000223732
Pedrosa, Erika ; Nolan, Karen A. ; Stefanescu, Radu ; Hershcovitz, Pnina ; Novak, Tomas ; Zukov, Ilja ; Stopkova, Pavla ; Lachman, Herbert M. / Analysis of a promoter polymorphism in the SMDF neuregulin 1 isoform in schizophrenia. In: Neuropsychobiology. 2009 ; Vol. 59, No. 4. pp. 205-212.
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