Association between golli-MBP and schizophrenia in the Jewish Ashkenazi population: are regulatory regions involved?
Int J Neuropsychopharmacol
; 12(7): 885-94, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19154657
ABSTRACT
Multiple studies have reported oligodendrocyte and myelin abnormalities, as well as dysregulation of their related genes, in brains of schizophrenia patients. One of these genes is the myelin-basic-protein (MBP) gene, which encodes two families of proteins classic-MBPs and golli-MBPs. While the classic-MBPs are predominantly located in the myelin sheaths of the nervous system, the golli proteins are more widely expressed and are found in both the immune and the nervous systems. In the present study we performed a case-control association analysis of golli-MBP in two separate Jewish Ashkenazi cohorts (cohort I 120 patients, 236 controls; cohort II 379 patients, 380 controls). In addition we performed an expression analysis of golli-MBP mRNA in post-mortem dorsolateral prefrontal cortex samples of schizophrenia patients, and matched controls. In the first cohort we observed association between six (out of 26 genotyped) single nucleotide polymorphisms (SNPs) and the disease (p<0.05). Of these, three are from one linkage disequilibrium (LD) block which contains a CTCF binding region. Haplotype analysis revealed significant 'risk'/'protective' haplotypes (strongest p=0.005, each) for schizophrenia. The three SNPs (rs12458282, rs2008323, rs721286) were then genotyped in the second cohort. The combined results showed strong effects, both in the single marker and in haplotype analyses (strongest OR 1.77, p=0.0005; OR 1.61, p=0.00001, respectively). Sequencing the CTCF binding region revealed three SNPs in complete LD with the associated haplotypes, located in close proximity to the CTCF binding site. Expression analysis found no significant differences in golli-MBP mRNA levels. These findings suggest that golli-MBP is a possible susceptibility gene for schizophrenia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Psicologia do Esquizofrênico
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Judeus
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Sequências Reguladoras de Ácido Nucleico
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Polimorfismo de Nucleotídeo Único
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Proteína Básica da Mielina
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Int J Neuropsychopharmacol
Assunto da revista:
NEUROLOGIA
/
PSICOFARMACOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Israel