Sex differences in GABAA receptor subunit transcript expression are mediated by genotype in subjects with alcohol-related cirrhosis of the liver.
Genes Brain Behav
; 21(4): e12785, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35301805
ABSTRACT
Male and female human subjects show contrasting propensities to misuse drugs of addiction, including alcohol. These differences lead to different psychological and neurological consequences, such as the likelihood of developing dependence. The pattern and extent of brain damage in alcohol-use disorder cases also varies with comorbid disease. To explore mechanisms that might underlie these outcomes, we used autopsy tissue to determine mRNA transcript expression in relation to genotype for two GABAA receptor subunit genes. We used quantitative Real-Time PCR to measure GABRA6 and GABRA2 mRNA concentrations in dorsolateral prefrontal and primary motor cortices of alcohol-use disorder subjects and controls of both sexes with and without liver disease who had been genotyped for these GABAA receptor subunit genes. Cirrhotic alcohol-use disorder cases had significantly higher expression of GABRA6 and GABRA2 transcripts than either controls or non-cirrhotic alcohol-use disorder cases. Differences were observed between sexes, genotypes and brain regions. We show that sex differences in subjects with GABRA6 and GABRA2 variants may contribute to differences in susceptibility to alcohol-use disorder and alcohol-induced cirrhosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de GABA-A
/
Alcoolismo
Limite:
Female
/
Humans
/
Male
Idioma:
En
Revista:
Genes Brain Behav
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
GENETICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália