Support for involvement of neuregulin 1 in schizophrenia pathophysiology.
Mol Psychiatry
; 10(4): 366-74, 328, 2005 Apr.
Article
in En
| MEDLINE
| ID: mdl-15545978
ABSTRACT
Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ("Hap(ICE)"), and two haplotypes located in the 3' end of NRG1 (all P<0.05). However, association was not detected with Hap(ICE) itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Schizophrenia
/
Chromosomes, Human, Pair 8
/
Neuregulin-1
/
Nerve Tissue Proteins
Type of study:
Clinical_trials
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2005
Document type:
Article
Affiliation country:
Estados Unidos