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Functional analysis of haplotypes and promoter activity at the 5' region of the human GABRB3 gene and associations with schizophrenia.
Mol Genet Genomic Med ; 7(5): e652, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30908890


This study investigated the effects of haplotypes T-G and C-A derived from NG_012836.1:g.4160T>C and NG_012836.1:g.4326G>A on protein expression levels in vitro and identified the functional sequence in the regulatory region of the GABRB3 gene linked to possible associations with schizophrenia.


Recombinant plasmids with haplotypes T-G and C-A and 10 recombinant vectors containing deletion fragments from the GABRB3 gene 5' regulatory region were transfected into HEK-293, SK-N-SH, and SH-SY5Y cells. The relative fluorescence intensity of the two haplotypes and different sequences was compared using a dual luciferase reporter assay system.


The relative fluorescence intensity of haplotype C-A was significantly lower than that of T-G. We shortened the core promoter sequence of the GABRB3 gene 5' regulation region from -177 bp to -18 bp (ATG+1). We also found an expression suppression region from -1,735 bp to -1,638 bp and an enhanced regulatory region from -1,638 bp to -1,335 bp. Multiple inhibitory functional elements were identified in the region from -680 bp to -177 bp.


We demonstrated that haplotype C-A might increase the risk of schizophrenia and found multiple regulatory regions that had an effect on GABRB3 receptor expression.





Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Esquizofrenia / Receptores de GABA-A Aspecto clínico: Etiologia Limite: Humanos Idioma: Inglês Revista: Mol Genet Genomic Med Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: China