Biomaterial Database

Analysis of GABRG2 C588T polymorphism in genetic epilepsy and evaluation of GABRG2 in drug treatment. 2021

Shitao Wang, and Xianjun Zhang, and Liang Zhou, and Qian Wu, and Yanbing Han

Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Epilepsy is a common disorder with complex inheritance, and its treatment is very unsatisfactory. An association between the GABRG2 C588T polymorphism and genetic generalized epilepsy has been studied by several genetic association studies. However, these results were inconsistent, and the role of GABRG2 in epilepsy treatment remains unknown. To evaluate the role of GABRG2 in epilepsy, we performed meta-analysis, expression quantitative trait loci analysis, protein-protein interaction analysis, and drug-gene interaction analysis. The combined results indicated that the GABRG2 C588T polymorphism was associated with genetic generalized epilepsy risk under dominant and allelic models (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.02-1.54, p = 0.03, I2 = 0% and OR = 1.21, 95% CI = 1.03-1.42, p = 0.02, I2 = 20%, respectively). In the Asian population, we also found similar results under dominant and allelic models (OR = 1.93, 95% CI = 1.18-3.16, p = 0.009, I2 = 0% and OR = 1.69, 95% CI = 1.20-2.37, p = 0.003, I2 = 11%, respectively). We first found that the GABRG2 C588T polymorphism regulates GABRG2 expression in human brain tissues and that the protein encoded by GABRG2 interacts with targets of approved antiepileptic drugs (AEDs). Interestingly, we also found that GABRG2 itself interacts with approved AEDs. Taken together, the results indicate that the C588T polymorphism might alter the GABAA receptor by modulating GABRG2 gene expression, resulting in increased risk for epilepsy, and that GABRG2 may be a potential therapeutic target for epilepsy.

UI	MeSH Term	Description	Entries
D011963	Receptors, GABA-A	Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.	Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D004829	Epilepsy, Generalized	Recurrent conditions characterized by epileptic seizures which arise diffusely and simultaneously from both hemispheres of the brain. Classification is generally based upon motor manifestations of the seizure (e.g., convulsive, nonconvulsive, akinetic, atonic, etc.) or etiology (e.g., idiopathic, cryptogenic, and symptomatic). (From Mayo Clin Proc, 1996 Apr;71(4):405-14)	Convulsive Generalized Seizure Disorder,Epilepsy, Tonic,Generalized Nonconvulsive Seizure Disorder,Seizure Disorder, Generalized,Convulsive Seizure Disorder, Generalized,Epilepsy, Akinetic,Epilepsy, Atonic,Generalized Convulsive Epilepsy,Generalized Nonconvulsive Epilepsy,Generalized Onset Seizure Disorder,Generalized Seizure Disorder, Convulsive,Generalized Seizure Disorder, Nonconvulsive,Nonconvulsive Generalized Seizure Disorder,Nonconvulsive Seizure Disorder, Generalized,Seizure Disorder, Convulsive, Generalized,Seizure Disorder, Generalized Nonconvulsive,Seizure Disorder, Generalized Onset,Seizure Disorder, Generalized, Convulsive,Seizure Disorder, Nonconvulsive Generalized,Symptomatic Generalized Epilepsy,Akinetic Epilepsies,Akinetic Epilepsy,Atonic Epilepsies,Atonic Epilepsy,Convulsive Epilepsies, Generalized,Convulsive Epilepsy, Generalized,Epilepsies, Akinetic,Epilepsies, Atonic,Epilepsies, Generalized,Epilepsies, Generalized Convulsive,Epilepsies, Tonic,Epilepsy, Generalized Convulsive,Epilepsy, Generalized Nonconvulsive,Epilepsy, Symptomatic Generalized,Generalized Convulsive Epilepsies,Generalized Epilepsies,Generalized Epilepsy,Generalized Epilepsy, Symptomatic,Generalized Seizure Disorder,Generalized Seizure Disorders,Nonconvulsive Epilepsy, Generalized,Seizure Disorders, Generalized,Tonic Epilepsies,Tonic Epilepsy
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483	Alleles	Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.	Allelomorphs,Allele,Allelomorph
D000927	Anticonvulsants	Drugs used to prevent SEIZURES or reduce their severity.	Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D016022	Case-Control Studies	Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time.	Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D044466	Asian People	Persons having origins in any of the Asian racial groups of the Far East, Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and Vietnam. Note that OMB category ASIAN is available for United States population groups. Race and ethnicity terms, as used in the federal government, are self-identified social construct and may include terms outdated and offensive in MeSH to assist users who are interested in retrieving comprehensive search results for studies such as in longitudinal studies.	Asian Continental Ancestry Group,Asian Person,Asiatic Race,Mongoloid Race,Asian Peoples,Asian Persons,Asiatic Races,Mongoloid Races,People, Asian,Person, Asian,Race, Asiatic,Race, Mongoloid
D056726	Genetic Association Studies	The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.	Candidate Gene Identification,Candidate Gene Analysis,Candidate Gene Association Studies,Candidate Gene Association Study,Gene Discovery,Genotype-Phenotype Association,Genotype-Phenotype Associations,Genotype-Phenotype Correlation,Genotype-Phenotype Correlations,Analyses, Candidate Gene,Analysis, Candidate Gene,Association Studies, Genetic,Association Study, Genetic,Association, Genotype-Phenotype,Associations, Genotype-Phenotype,Candidate Gene Analyses,Correlation, Genotype-Phenotype,Correlations, Genotype-Phenotype,Discovery, Gene,Gene Analyses, Candidate,Gene Analysis, Candidate,Gene Identification, Candidate,Genetic Association Study,Genotype Phenotype Association,Genotype Phenotype Associations,Genotype Phenotype Correlation,Genotype Phenotype Correlations,Identification, Candidate Gene,Studies, Genetic Association,Study, Genetic Association
D060066	Protein Interaction Maps	Graphs representing sets of measurable, non-covalent physical contacts with specific PROTEINS in living organisms or in cells.	Protein-Protein Interaction Map,Protein-Protein Interaction Network,Protein Interaction Networks,Interaction Map, Protein,Interaction Map, Protein-Protein,Interaction Network, Protein,Interaction Network, Protein-Protein,Map, Protein Interaction,Map, Protein-Protein Interaction,Network, Protein Interaction,Network, Protein-Protein Interaction,Protein Interaction Map,Protein Interaction Network,Protein Protein Interaction Map,Protein Protein Interaction Network,Protein-Protein Interaction Maps,Protein-Protein Interaction Networks