Document Detail


Association of RGS2 and RGS5 variants with schizophrenia symptom severity.
MedLine Citation:
PMID:  18262772     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Several lines of evidence indicate that Regulator of G Protein Signaling 4 (RGS4) contributes to schizophrenia vulnerability. RGS4 is one of a family of molecules that modulate signaling via G-protein coupled receptors. Five genes encoding members of this family (RGS2, RGS4, RGS5, RGS8 and RGS16) map to chromosome 1q23.3-1q31. Due to overlapping cellular functions and chromosomal proximity, we hypothesized that multiple RGS genes may contribute to schizophrenia severity and treatment responsiveness.
METHODS: Subjects were 750 individuals with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Inferred ancestries were: 221 (30%) 'Africa only', 422 (56%) 'Europe only' and 107 (14%) 'Other'. Fifty-nine single nucleotide polymorphisms (SNPs) in or near the RGS5, RGS16, RGS8 and RGS2 genes were genotyped. Multiple linear regression was used to analyze association of markers with Positive and Negative Symptoms Scale (PANSS) total scores at baseline and throughout antipsychotic treatment.
RESULTS: RGS5 marker rs10799902 was associated with altered baseline PANSS total score in both the Africa only (P=0.0440) and Europe only (P=0.0143) strata, although neither association survived multiple comparisons correction. A common five-marker haplotype of the RGS2 gene was associated with more severe baseline PANSS total score in the Europe only strata (global P=0.0254; haplotype-specific P=0.0196). In contrast to RGS4, none of the markers showed association with antipsychotic treatment response.
CONCLUSIONS: RGS2 and RGS5 genotypes predicted severity of baseline symptoms in schizophrenia. Although these analyses are exploratory and replication is required, these data suggest a possible role for multiple RGS proteins in schizophrenia.
Authors:
Daniel B Campbell; Leslie A Lange; Tara Skelly; Jeffrey Lieberman; Pat Levitt; Patrick F Sullivan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-02-11
Journal Detail:
Title:  Schizophrenia research     Volume:  101     ISSN:  0920-9964     ISO Abbreviation:  Schizophr. Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-05-02     Completed Date:  2008-08-13     Revised Date:  2014-09-09    
Medline Journal Info:
Nlm Unique ID:  8804207     Medline TA:  Schizophr Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  67-75     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
African Continental Ancestry Group
Aged
Analysis of Variance
European Continental Ancestry Group
Female
Gene Frequency
Genetic Predisposition to Disease*
Genotype
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide
Psychiatric Status Rating Scales
RGS Proteins / genetics*
Schizophrenia / genetics*
Grant Support
ID/Acronym/Agency:
MH45156/MH/NIMH NIH HHS; P30 HD015052/HD/NICHD NIH HHS; P30 HD015052-27S1/HD/NICHD NIH HHS; P30 HD15052/HD/NICHD NIH HHS; P50 MH045156/MH/NIMH NIH HHS; P50 MH045156-18/MH/NIMH NIH HHS; R01 MH-074027/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/RGS Proteins; 0/RGS2 protein, human; 0/RGS5 protein, human
Comments/Corrections

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