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Sequence Variation Associated with SLC12A5 Gene Expression Is Linked to Brain Structure and Function in Healthy Adults.
Gregory, Michael D; Kippenhan, J Shane; Callicott, Joseph H; Rubinstein, Daniel Y; Mattay, Venkata S; Coppola, Richard; Berman, Karen F.
Afiliación
  • Gregory MD; Section on Integrative Neuroimaging, Clinical and Translational Neuroscience Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
  • Kippenhan JS; Section on Integrative Neuroimaging, Clinical and Translational Neuroscience Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
  • Callicott JH; Psychosis and Cognitive Studies Section, Clinical and Translational Neuroscience Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
  • Rubinstein DY; Section on Integrative Neuroimaging, Clinical and Translational Neuroscience Branch, National Institute of Mental Health Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.
  • Mattay VS; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
  • Coppola R; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Berman KF; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cereb Cortex ; 29(11): 4654-4661, 2019 12 17.
Article en En | MEDLINE | ID: mdl-30668668
A single-nucleotide polymorphism in the promoter region of the Matrix Metalloproteinase-9 (MMP9) gene, rs3918242, has been shown to affect MMP9 expression in macrophages and was associated with schizophrenia by two independent groups. However, rs3918242's effects on MMP9 expression were not replicable in cell lines or brain tissue. Additionally, publically available data indicate that rs3918242 genotype is related not to MMP9 expression, but rather to expression of SLC12A5, a nearby gene coding for a K+/Cl- cotransporter, whose expression has also been related to schizophrenia. Here, we studied brain structure and function in healthy participants stratified by rs3918242 genotype using structural MRI (N = 298), functional MRI during an N-back working memory task (N = 554), and magnetoencephalography (MEG) during the same task (N = 190). We found rs3918242 was associated with gray matter volume (GMV) in the insula and dorsolateral prefrontal cortex bilaterally, closely replicated in discovery and replication samples; and with inferior parietal lobule (IPL) GMV when the samples were meta-analytically combined. Additionally, using both fMRI and MEG, rs3918242 was associated with right IPL working memory-related activation, replicated in two cohorts and across imaging modalities. These convergent results provide further impetus for examinations of the relationship of SLC12A5 with brain structure and function in neuropsychiatric disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Expresión Génica / Simportadores Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Expresión Génica / Simportadores Tipo de estudio: Risk_factors_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: Cereb Cortex Asunto de la revista: CEREBRO Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos