Sex differences in GABA A receptor subunit transcript expression are mediated by genotype in subjects with alcohol‐related cirrhosis of the liver
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 disord...
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| Published in | Genes, brain and behavior Vol. 21; no. 4; p. e12785 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
01.04.2022
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1601-1848 1601-183X |
| DOI | 10.1111/gbb.12785 |
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| 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 GABA
A
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 GABA
A
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. |
|---|---|
| AbstractList | 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 GABA
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 GABA
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. 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 GABA A 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 GABA A 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. |
| Author | Ashton, Madeline K. Stadlin, Alfreda Noor Aizin, Noradibah Arina Binte M. Dodd, Peter R. Ho, Ada M.‐C. Sharma, Hansa Rueda, André V. L. Camarini, Rosana |
| Author_xml | – sequence: 1 givenname: Madeline K. surname: Ashton fullname: Ashton, Madeline K. organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia – sequence: 2 givenname: André V. L. orcidid: 0000-0003-4581-8992 surname: Rueda fullname: Rueda, André V. L. organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia, Departamento de Farmacologia, ICB Universidade de São Paulo São Paulo Brazil – sequence: 3 givenname: Ada M.‐C. orcidid: 0000-0003-4989-8782 surname: Ho fullname: Ho, Ada M.‐C. organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia, Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota USA – sequence: 4 givenname: Noradibah Arina Binte M. surname: Noor Aizin fullname: Noor Aizin, Noradibah Arina Binte M. organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia, Vela Research Singapore Pte Ltd The Kendall Singapore – sequence: 5 givenname: Hansa surname: Sharma fullname: Sharma, Hansa organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia – sequence: 6 givenname: Peter R. orcidid: 0000-0001-5970-0181 surname: Dodd fullname: Dodd, Peter R. organization: School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Queensland Australia – sequence: 7 givenname: Alfreda orcidid: 0000-0002-7231-5832 surname: Stadlin fullname: Stadlin, Alfreda organization: College of Medicine Ajman University Ajman UAE – sequence: 8 givenname: Rosana orcidid: 0000-0002-8131-6108 surname: Camarini fullname: Camarini, Rosana organization: Departamento de Farmacologia, ICB Universidade de São Paulo São Paulo Brazil |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35301805$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3390_brainsci14060610 crossref_primary_10_1016_j_alcohol_2024_06_005 crossref_primary_10_1159_000533946 crossref_primary_10_14309_ajg_0000000000003086 crossref_primary_10_2147_RMHP_S483830 |
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| Keywords | alcohol misuse human brain genotype-phenotype interactions qRT-PCR |
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| SubjectTerms | Alcoholism - genetics Alcoholism - metabolism Female Genotype Humans Liver Cirrhosis - genetics Male Polymorphism, Single Nucleotide Receptors, GABA-A - genetics Sex Characteristics |
| Title | Sex differences in GABA A receptor subunit transcript expression are mediated by genotype in subjects with alcohol‐related cirrhosis of the liver |
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