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GABRB2

This article was updated by an external expert under a dual publication model. The corresponding peer-reviewed article was published in the journal Gene. Click to view.
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GABRB2
Identifiers
AliasesGABRB2, gamma-aminobutyric acid type A receptor beta2 subunit, ICEE2, gamma-aminobutyric acid type A receptor subunit beta2, DEE92
External IDsOMIM: 600232; MGI: 95620; HomoloGene: 7327; GeneCards: GABRB2; OMA:GABRB2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2561

14401

Ensembl

ENSG00000145864

ENSMUSG00000007653

UniProt

P47870

P63137

RefSeq (mRNA)

NM_000813
NM_021911
NM_001371727

NM_008070
NM_001347314
NM_001362646
NM_001362647
NM_001362649

RefSeq (protein)

NP_000804
NP_068711
NP_001358656

NP_001334243
NP_032096
NP_001349575
NP_001349576
NP_001349578

Location (UCSC)Chr 5: 161.29 – 161.55 MbChr 11: 42.31 – 42.52 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The GABAA beta-2 subunit is a protein that in humans is encoded by the GABRB2 gene. It combines with other subunits to form the ionotropic GABAA receptors. GABA (γ-aminobutyric acid) system is the major inhibitory system in the brain, and its dominant GABAA receptor subtype is composed of α1, β2, and γ2 subunits with the stoichiometry of 2:2:1, which accounts for 43% of all GABAA receptors.[5][6] Alternative splicing of the GABRB2 gene leads at least to four isoforms, viz. β2-long (β2L) and β2-short (β2S, β2S1, and β2S2). Alternatively spliced variants displayed similar but non-identical electrophysiological properties.[7] GABRB2 is subjected to positive selection and known to be both an alternative splicing and a recombination hotspot; it is regulated via epigenetic regulation including imprinting and gene and promoter methylation [8][9][10] GABRB2 has been associated with a number of neuropsychiatric disorders, and found to display altered expression in cancer.

Structure

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GABRB2 encodes the GABAA receptor beta-2 subunit. It is highly expressed in the brain with dominance in the gray matter.[11] In humans, it is located on chromosome 5q34, with 11 exons and 10 introns spanning more than 260 kb, and a promoter region ranging from 1000 bp upstream to 689 bp downstream of exon 1.[12] Alternative splicing of the gene product yields at least four isoforms, viz. β2-long (β2L), β2-short (β2S) and two additional short isoforms β2S1 and β2S2. These isoforms, composed of 512, 474, 313, and 372 amino acids respectively,[13] display dissimilar electrophysiological properties.[11] In mice, the corresponding Gabrb2 gene on chromosome 11A5 comprises 12 exons and 11 introns, and the two isoforms β2L and β2S from alternative splicing consisted of 512 and 474 amino acids respectively.[14] The β-2 subunit is a component of the ligand-gated chloride GABAA receptors which belongs to the Cys-loop superfamily.[15] Like all subunits of this family, it consists of an extracellular N-terminal domain containing a Cys-loop of 13 amino acids, four membrane-spanning domains (TM1-4) with a large intracellular loop between TM3 and TM4, and an extracellular C-terminal domain.[16] Five subunits from varied families (α1-6, β1-3, γ1-3, δ, ε, π, θ, ρ1-3) combine to form the heteropentameric GABAA receptor. TM2 from each subunit participates in the formation of the ion pore of the receptor, and α2β2γ2 is the major subtype in the brain that accounts for 43% of all GABAA receptors.[17][5]

Regulation

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Phosphorylation is an important mechanism for the modulation of GABAA receptor function.[18] GABRB2 includes a consensus sequence for a calmodulin-dependent protein kinase II within exon 10 which is only expressed by β2L. As a result, upon repetitive stimulation, the β2L isoform-containing GABAA receptors are more vulnerable to run-down than those containing the short isoforms. Accordingly, ATP depletion reduces the inhibitory transmission of the GABAergic system due to GABAA receptors rundown through β2. Since this rundown occasioned by the presence of β2L would lead to improved maintenance of survival-favoring activities such as hunting and food gathering in the face of energy deprivation, it could be selected as an evolutionary advantage over the shorter isoforms.[19][8][11] Multiple lines of evidence confirmed the epigenetic regulation of GABRB2 gene expression via methylation and imprinting. GABRB2 mRNA expression level varied with germline genotypes, and with the gender of the parent in accord with the process of imprinting.[9][20][10][21]

Function

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GABRB2 is highly expressed in the brain where it plays its major role.[22] In the immature brain, GABAA receptors participate in excitatory transmission,[23] which is important to synaptogenesis, neurogenesis, and the formation of the glutamatergic system.[24] In the mature brain, GABAA receptors fulfill their conventional inhibitory role, with the β2 subunits participating in some of the fastest inhibitory transmissions that prevent hyperexcitability, regulate the stress response of the hypothalamic-pituitary-adrenal axis, as well as pain signals mediated by the thalamus.[25][26] Moreover, GABRB2 is associated with cognitive function, energy regulation, time perception,[27] and the maintenance of efferent synaptic terminals in the mature ear.[28]

Clinical significance

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GABRB2 is associated with a spectrum of neuropsychiatric disorders, and displays of differential gene expression between tumor and non tumor tissues.

Psychiatric disorders

[edit]

Schizophrenia

[edit]

Single nucleotide polymorphisms (SNPs) in GABRB2 were first associated with schizophrenia (SCZ) in Han Chinese, and confirmed subsequently for German, Portuguese, and Japanese SCZ patients.[29][30][31][32][33] Furthermore, their significant associations have been extended to cognitive function, psychosis, and neuroleptic-induced tardive dyskinesia in schizophrenics.[34][35][36] Recurrent copy number variations (CNVs) in GABRB2 were likewise associated with schizophrenia.[37] GABRB2 expression was decreased in genotype and age-dependent manners, with reduced β2L/β2S ratios in schizophrenics serving as a key determinant of the response of receptor function to the energy status.[11][8] The regulation of its expression by methylation and imprinting,[9][10][21] as well as its N-glycosylation of the β2-subunit, were altered in SCZ.[38] That GABRB2 is both a recombination hotspot and subject to positive selection could be an important factor in the widespread occurrence of SCZ.[8] Gabrb2-knockout mice displayed schizophrenia-like behavior including prepulse inhibition deficit and antisocial behavior that were ameliorated by the antipsychotic risperidone, strongly supporting the proposal based on postmortem SCZ brains that GABRB2 represents the key genetic factor in SCZ etiology.[39]

Other psychiatric disorders

[edit]

GABRB2 was significantly associated with bipolar disorder, with a genotype-dependent decrease in GABRB2 mRNA levels weaker than that observed in SCZ.[7][40][41][42] In major depressive disorder, the expressions of GABAA subunit genes were altered,[43] and the expression of GABRB2 was significantly decreased in the anterior cingulate cortex, in the postmortem brains of patients.[44] The expression of GABRB2 was significantly increased in the internet gaming disorder group, and GABRB2 was the downstream target for two circulating microRNA, viz. hsa-miR-26b-5p and hsa-miR-652-3p, which were significantly downregulated in these subjects.[45] The GABAergic system was suggested to be a factor in the physiopathology of premenstrual dysphoric disorder (PMDD).[46] GABA levels were altered in the brain of PMDD patients.[47] Two highly recurrent copy number variations in GABRB2 were associated with PMDD in Chinese and German patients, providing thereby a possible explanation of part of the complex psychological symptoms of PMDD.[37]

Drug dependence

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SNPs in GABRB2 were significantly associated with alcohol dependence and consumption in Southwestern Native Americans, Finnish, Scottish, and Sidney populations.[48][49][50] Chronic alcohol administration induced an increase in the expression of Gabrb2 in a rat model.[51] and sleep time was decreased in Gabrb2 knockout mice.[52] SNPs in GABRB2 were significantly associated with heroin addiction in African American subjects.[53] Haplotypes in GABRB2 yielded a significant association with heroin dependence in the Chinese population.[54]

Neurological disorders

[edit]

Epilepsy

[edit]

Numerous de novo mutations in GABRB2 were associated with infantile and early childhood epileptic encephalopathy (IECEE).[55][56][57][58][59] As well, SNPs in GABRB2 were significantly associated with epilepsy in the North Indian population.[60] Moreover, Gabrb2 knockout mice displayed audiogenic epilepsy, which further confirmed the contribution of GABRB2 to the etiology of epilepsy.[39]

Autism spectrum disorder

[edit]

The density of GABAA receptors showed a significant reduction in autistic brains.[61] and SNPs in GABRB2 were significantly associated with autism.[62] De novo pathogenic mutations in the GABRB2 gene contribute to the physiopathology of Rett syndrome.[63][64] β2 subunit mRNA expression level was subjected to significant upregulation in a mouse model of Rett syndrome [65]

Neurodegenerative disorders

[edit]

Deficits in the GABergic system and decreased levels of GABA were reported in Alzheimer's disease (AD).[66] An SNP near GABRB2 was associated with AD.[67] Two SNPs in GABRB2 were significantly associated with frontotemporal dementia (FTD) risk, and GABRB2 was downregulated in a cellular system of FTD and a mouse model of tauopathy.[68][69]

Cancer

[edit]

Genomic classifiers including GABRB2 could differentiate correctly between malignant and benign nodules.[70][71] and GABRB2 alone or in combination with other genes correctly distinguished between malignant and benign tumors.[72][73] GABRB2 was upregulated and hypomethylated in papillary thyroid carcinoma. The downregulation of GABRB2 enhanced the apoptotic cell death and decreased proliferation, migration, and invasiveness of thyroid cancer cells.[74][75] GABRB2 was upregulated in adrenocortical carcinoma and salivary gland cancer,[76][77] but downregulated in patients with colorectal cancer, brain tumors, kidney renal clear cell carcinoma and lung cancer [78][79][80][81][82][83]

Therapeutic implications

[edit]

The β2 subunit-containing GABAA receptors are more sensitive to GABA.[84] Tyrosine and proline residues in the Cys-loop of this subunit were important elements in the binding and response to GABA,[85][86] and the subunit also mediated the receptor binding of alcohol and anesthetics, anticonvulsive activity of loreclezole, hypothermic response to etomidate, as well as the sedative effects of both etomidate and loreclezole.[6][87][88] It was identified as a target for the endocannabinoid 2-arachidonylglycerol,[89] and Gabrb2 expression was upregulated by the antiepileptic drug qingyangshenylycosides and downregulated by the opioid oxycodone [90][91] The wide-ranging involvement of the GABRB2 and its gene products in neuropsychiatric pharmacology are in accord with their central roles in inhibitory signaling in the brain.

See also

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Notes

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References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145864 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000007653 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b McKernan RM, Whiting PJ (April 1996). "Which GABAA-receptor subtypes really occur in the brain?". Trends in Neurosciences. 19 (4): 139–43. doi:10.1016/s0166-2236(96)80023-3. PMID 8658597. S2CID 4970577.
  6. ^ a b McCracken ML, Borghese CM, Trudell JR, Harris RA (December 2010). "A transmembrane amino acid in the GABAA receptor β2 subunit critical for the actions of alcohols and anesthetics". The Journal of Pharmacology and Experimental Therapeutics. 335 (3): 600–6. doi:10.1124/jpet.110.170472. PMC 2993559. PMID 20826568.
  7. ^ a b Zhao C, Xu Z, Wang F, Chen J, Ng SK, Wong PW, et al. (September 2009). "Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders". PLOS ONE. 4 (9): e6977. Bibcode:2009PLoSO...4.6977Z. doi:10.1371/journal.pone.0006977. PMC 2741204. PMID 19763268.
  8. ^ a b c d Lo WS, Xu Z, Yu Z, Pun FW, Ng SK, Chen J, et al. (May 2007). "Positive selection within the Schizophrenia-associated GABA(A) receptor beta(2) gene". PLOS ONE. 2 (5): e462. Bibcode:2007PLoSO...2..462L. doi:10.1371/journal.pone.0000462. PMC 1866178. PMID 17520021.
  9. ^ a b c Pun FW, Zhao C, Lo WS, Ng SK, Tsang SY, Nimgaonkar V, et al. (May 2011). "Imprinting in the schizophrenia candidate gene GABRB2 encoding GABA(A) receptor β(2) subunit". Molecular Psychiatry. 16 (5): 557–68. doi:10.1038/mp.2010.47. PMID 20404824. S2CID 11923808.
  10. ^ a b c Zhao C, Wang F, Pun FW, Mei L, Ren L, Yu Z, et al. (February 2012). "Epigenetic regulation on GABRB2 isoforms expression: developmental variations and disruptions in psychotic disorders". Schizophrenia Research. 134 (2–3): 260–6. doi:10.1016/j.schres.2011.11.029. PMID 22206711. S2CID 20093711.
  11. ^ a b c d Zhao C, Xu Z, Chen J, Yu Z, Tong KL, Lo WS, et al. (December 2006). "Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia". Molecular Psychiatry. 11 (12): 1092–105. doi:10.1038/sj.mp.4001899. PMID 16983389. S2CID 43731952.
  12. ^ "GABRB2 gamma-aminobutyric acid type A receptor subunit beta2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov.
  13. ^ "GABRB2 - Gamma-aminobutyric acid receptor subunit beta-2 precursor - Homo sapiens (Human) - GABRB2 gene & protein". www.uniprot.org.
  14. ^ "Gabrb2 - Gamma-aminobutyric acid receptor subunit beta-2 precursor - Mus musculus (Mouse) - Gabrb2 gene & protein". www.uniprot.org.
  15. ^ Hirose S (2014). "Mutant GABAA receptor subunits in genetic (Idiopathic) epilepsy". Mutant GABA(A) receptor subunits in genetic (idiopathic) epilepsy. Progress in Brain Research. Vol. 213. pp. 55–85. doi:10.1016/B978-0-444-63326-2.00003-X. ISBN 978-0-444-63326-2. PMID 25194483.
  16. ^ Cheng J, Ju XL, Chen XY, Liu GY (September 2009). "Homology modeling of human alpha 1 beta 2 gamma 2 and house fly beta 3 GABA receptor channels and Surflex-docking of fipronil". Journal of Molecular Modeling. 15 (9): 1145–53. doi:10.1007/s00894-009-0477-2. PMID 19238461. S2CID 4710128.
  17. ^ Houston CM, Lee HH, Hosie AM, Moss SJ, Smart TG (June 2007). "Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors". The Journal of Biological Chemistry. 282 (24): 17855–65. doi:10.1074/jbc.M611533200. PMID 17442679. S2CID 3194601.
  18. ^ Baumann SW, Baur R, Sigel E (November 2002). "Forced subunit assembly in alpha1beta2gamma2 GABAA receptors. Insight into the absolute arrangement". The Journal of Biological Chemistry. 277 (48): 46020–5. doi:10.1074/jbc.M207663200. PMID 12324466.
  19. ^ Palma E, Ragozzino DA, Di Angelantonio S, Spinelli G, Trettel F, Martinez-Torres A, et al. (July 2004). "Phosphatase inhibitors remove the run-down of gamma-aminobutyric acid type A receptors in the human epileptic brain". Proceedings of the National Academy of Sciences of the United States of America. 101 (27): 10183–8. Bibcode:2004PNAS..10110183P. doi:10.1073/pnas.0403683101. PMC 454185. PMID 15218107.
  20. ^ Wang L, Jiang W, Lin Q, Zhang Y, Zhao C (November 2016). "DNA methylation regulates gabrb2 mRNA expression: developmental variations and disruptions in l-methionine-induced zebrafish with schizophrenia-like symptoms". Genes, Brain and Behavior. 15 (8): 702–710. doi:10.1111/gbb.12315. PMID 27509263. S2CID 28530783.
  21. ^ a b Zong L, Zhou L, Hou Y, Zhang L, Jiang W, Zhang W, et al. (May 2017). "Genetic and epigenetic regulation on the transcription of GABRB2: Genotype-dependent hydroxymethylation and methylation alterations in schizophrenia". Journal of Psychiatric Research. 88: 9–17. doi:10.1016/j.jpsychires.2016.12.019. PMID 28063323.
  22. ^ Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. (February 2014). "Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics". Molecular & Cellular Proteomics. 13 (2): 397–406. doi:10.1074/mcp.M113.035600. PMC 3916642. PMID 33498127. S2CID 24894231.
  23. ^ Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R (October 2007). "GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations". Physiological Reviews. 87 (4): 1215–84. doi:10.1152/physrev.00017.2006. PMID 17928584.
  24. ^ Chen G, Trombley PQ, van den Pol AN (October 1995). "GABA receptors precede glutamate receptors in hypothalamic development; differential regulation by astrocytes". Journal of Neurophysiology. 74 (4): 1473–84. doi:10.1152/jn.1995.74.4.1473. PMID 8989386.
  25. ^ Zhang Q, Long Q, Ott J (June 2014). "AprioriGWAS, a new pattern mining strategy for detecting genetic variants associated with disease through interaction effects". PLOS Computational Biology. 10 (6): e1003627. Bibcode:2014PLSCB..10E3627Z. doi:10.1371/journal.pcbi.1003627. PMC 4046917. PMID 24901472.
  26. ^ Herman JP, Mueller NK, Figueiredo H (June 2004). "Role of GABA and glutamate circuitry in hypothalamo-pituitary-adrenocortical stress integration". Annals of the New York Academy of Sciences. 1018 (1): 35–45. Bibcode:2004NYASA1018...35H. doi:10.1196/annals.1296.004. PMID 15240350. S2CID 41508331.
  27. ^ Marinho V, Oliveira T, Bandeira J, Pinto GR, Gomes A, Lima V, et al. (August 2018). "Genetic influence alters the brain synchronism in perception and timing". Journal of Biomedical Science. 25 (1): 61. doi:10.1186/s12929-018-0463-z. PMC 6080374. PMID 30086746.
  28. ^ Maison SF, Rosahl TW, Homanics GE, Liberman MC (October 2006). "Functional role of GABAergic innervation of the cochlea: phenotypic analysis of mice lacking GABA(A) receptor subunits alpha 1, alpha 2, alpha 5, alpha 6, beta 2, beta 3, or delta". The Journal of Neuroscience. 26 (40): 10315–26. doi:10.1523/JNEUROSCI.2395-06.2006. PMC 1806703. PMID 17021187.
  29. ^ Lo WS, Lau CF, Xuan Z, Chan CF, Feng GY, He L, et al. (June 2004). "Association of SNPs and haplotypes in GABAA receptor beta2 gene with schizophrenia". Molecular Psychiatry. 9 (6): 603–8. doi:10.1038/sj.mp.4001461. PMID 14699426. S2CID 5567422.
  30. ^ Liu J, Shi Y, Tang W, Guo T, Li D, Yang Y, et al. (September 2005). "Positive association of the human GABA-A-receptor beta 2 subunit gene haplotype with schizophrenia in the Chinese Han population". Biochemical and Biophysical Research Communications. 334 (3): 817–23. doi:10.1016/j.bbrc.2005.06.167. PMID 16023997.
  31. ^ Lo WS, Harano M, Gawlik M, Yu Z, Chen J, Pun FW, et al. (March 2007). "GABRB2 association with schizophrenia: commonalities and differences between ethnic groups and clinical subtypes". Biological Psychiatry. 61 (5): 653–60. doi:10.1016/j.biopsych.2006.05.003. PMID 16950232. S2CID 25363556.
  32. ^ Petryshen TL, Middleton FA, Tahl AR, Rockwell GN, Purcell S, Aldinger KA, et al. (December 2005). "Genetic investigation of chromosome 5q GABAA receptor subunit genes in schizophrenia". Molecular Psychiatry. 10 (12): 1074–88, 1057. doi:10.1038/sj.mp.4001739. PMID 16172613. S2CID 22447580.
  33. ^ Yu Z, Chen J, Shi H, Stoeber G, Tsang SY, Xue H (March 2006). "Analysis of GABRB2 association with schizophrenia in German population with DNA sequencing and one-label extension method for SNP genotyping". Clinical Biochemistry. 39 (3): 210–8. doi:10.1016/j.clinbiochem.2006.01.009. PMID 16472798.
  34. ^ Tsang SY, Zhong S, Mei L, Chen J, Ng SK, Pun FW, et al. (24 April 2013). "Social cognitive role of schizophrenia candidate gene GABRB2". PLOS ONE. 8 (4): e62322. Bibcode:2013PLoSO...862322T. doi:10.1371/journal.pone.0062322. PMC 3634734. PMID 23638040.
  35. ^ Zhang Q, Zhang X, Song S, Wang S, Wang X, Yu H, et al. (June 2020). "The association of GABRB2 SNPs with cognitive function in schizophrenia". European Archives of Psychiatry and Clinical Neuroscience. 270 (4): 443–449. doi:10.1007/s00406-019-00985-3. PMID 30706170. S2CID 59524699.
  36. ^ Inada T, Koga M, Ishiguro H, Horiuchi Y, Syu A, Yoshio T, et al. (April 2008). "Pathway-based association analysis of genome-wide screening data suggest that genes associated with the gamma-aminobutyric acid receptor signaling pathway are involved in neuroleptic-induced, treatment-resistant tardive dyskinesia". Pharmacogenetics and Genomics. 18 (4): 317–23. doi:10.1097/FPC.0b013e3282f70492. PMID 18334916. S2CID 13053983.
  37. ^ a b Ullah A, Long X, Mat WK, Hu T, Khan MI, Hui L, et al. (30 June 2020). "Highly Recurrent Copy Number Variations in GABRB2 Associated With Schizophrenia and Premenstrual Dysphoric Disorder". Frontiers in Psychiatry. 11: 572. doi:10.3389/fpsyt.2020.00572. PMC 7338560. PMID 32695026.
  38. ^ Mueller TM, Haroutunian V, Meador-Woodruff JH (February 2014). "N-Glycosylation of GABAA receptor subunits is altered in Schizophrenia". Neuropsychopharmacology. 39 (3): 528–37. doi:10.1038/npp.2013.190. PMC 3895232. PMID 23917429.
  39. ^ a b Yeung RK, Xiang ZH, Tsang SY, Li R, Ho TY, Li Q, et al. (July 2018). "Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron-astrocyte-microglia dysregulation". Translational Psychiatry. 8 (1): 128. doi:10.1038/s41398-018-0176-9. PMC 6048160. PMID 30013074.
  40. ^ Perlis RH, Purcell S, Fagerness J, Kirby A, Petryshen TL, Fan J, et al. (January 2008). "Family-based association study of lithium-related and other candidate genes in bipolar disorder". Archives of General Psychiatry. 65 (1): 53–61. doi:10.1001/archgenpsychiatry.2007.15. PMID 18180429.
  41. ^ Breuer R, Hamshere ML, Strohmaier J, Mattheisen M, Degenhardt F, Meier S, et al. (June 2011). "Independent evidence for the selective influence of GABA(A) receptors on one component of the bipolar disorder phenotype". Molecular Psychiatry. 16 (6): 587–9. doi:10.1038/mp.2010.67. PMID 20548298. S2CID 21136441.
  42. ^ Chen J, Tsang SY, Zhao CY, Pun FW, Yu Z, Mei L, et al. (December 2009). "GABRB2 in schizophrenia and bipolar disorder: disease association, gene expression and clinical correlations". Biochemical Society Transactions. 37 (Pt 6): 1415–8. doi:10.1042/BST0371415. PMID 19909288. S2CID 10742771.
  43. ^ Choudary PV, Molnar M, Evans SJ, Tomita H, Li JZ, Vawter MP, et al. (October 2005). "Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression". Proceedings of the National Academy of Sciences of the United States of America. 102 (43): 15653–8. Bibcode:2005PNAS..10215653C. doi:10.1073/pnas.0507901102. PMC 1257393. PMID 16230605.
  44. ^ Zhao J, Bao AM, Qi XR, Kamphuis W, Luchetti S, Lou JS, et al. (May 2012). "Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of non-suicidal elderly depressed patients". Journal of Affective Disorders. 138 (3): 494–502. doi:10.1016/j.jad.2012.01.013. PMID 22357337.
  45. ^ Lee M, Cho H, Jung SH, Yim SH, Cho SM, Chun JW, et al. (12 March 2018). "Circulating MicroRNA Expression Levels Associated With Internet Gaming Disorder". Frontiers in Psychiatry. 9: 81. doi:10.3389/fpsyt.2018.00081. PMC 5858605. PMID 29593587.
  46. ^ Hofmeister S, Bodden S (August 2016). "Premenstrual Syndrome and Premenstrual Dysphoric Disorder". American Family Physician. 94 (3): 236–40. PMID 27479626.
  47. ^ Liu B, Wang G, Gao D, Gao F, Zhao B, Qiao M, et al. (January 2015). "Alterations of GABA and glutamate-glutamine levels in premenstrual dysphoric disorder: a 3T proton magnetic resonance spectroscopy study". Psychiatry Research. 231 (1): 64–70. doi:10.1016/j.pscychresns.2014.10.020. hdl:1959.4/unsworks_13100. PMID 25465316. S2CID 16186822.
  48. ^ Tabakoff B, Saba L, Printz M, Flodman P, Hodgkinson C, Goldman D, et al. (October 2009). "Genetical genomic determinants of alcohol consumption in rats and humans". BMC Biology. 7 (1): 70. doi:10.1186/1741-7007-7-70. PMC 2777866. PMID 19874574.
  49. ^ Loh EW, Smith I, Murray R, McLaughlin M, McNulty S, Ball D (November 1999). "Association between variants at the GABAAbeta2, GABAAalpha6 and GABAAgamma2 gene cluster and alcohol dependence in a Scottish population". Molecular Psychiatry. 4 (6): 539–44. doi:10.1038/sj.mp.4000554. PMID 10578235. S2CID 23865925.
  50. ^ Radel M, Vallejo RL, Iwata N, Aragon R, Long JC, Virkkunen M, et al. (January 2005). "Haplotype-based localization of an alcohol dependence gene to the 5q34 {gamma}-aminobutyric acid type A gene cluster". Archives of General Psychiatry. 62 (1): 47–55. doi:10.1001/archpsyc.62.1.47. PMID 15630072.
  51. ^ Devaud LL, Fritschy JM, Sieghart W, Morrow AL (July 1997). "Bidirectional alterations of GABA(A) receptor subunit peptide levels in rat cortex during chronic ethanol consumption and withdrawal". Journal of Neurochemistry. 69 (1): 126–30. doi:10.1046/j.1471-4159.1997.69010126.x. PMID 9202302. S2CID 19820284.
  52. ^ Blednov YA, Jung S, Alva H, Wallace D, Rosahl T, Whiting PJ, et al. (January 2003). "Deletion of the alpha1 or beta2 subunit of GABAA receptors reduces actions of alcohol and other drugs". The Journal of Pharmacology and Experimental Therapeutics. 304 (1): 30–6. doi:10.1124/jpet.102.042960. PMID 12490572. S2CID 1846375.
  53. ^ Levran O, Peles E, Randesi M, Correa da Rosa J, Ott J, Rotrosen J, et al. (January 2016). "Glutamatergic and GABAergic susceptibility loci for heroin and cocaine addiction in subjects of African and European ancestry". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 64: 118–23. doi:10.1016/j.pnpbp.2015.08.003. PMC 4564302. PMID 26277529.
  54. ^ Kim YS, Yang M, Mat WK, Tsang SY, Su Z, Jiang X, et al. (12 November 2015). "GABRB2 Haplotype Association with Heroin Dependence in Chinese Population". PLOS ONE. 10 (11): e0142049. Bibcode:2015PLoSO..1042049K. doi:10.1371/journal.pone.0142049. PMC 4643001. PMID 26561861.
  55. ^ Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, et al. (November 2017). "High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies". American Journal of Human Genetics. 101 (5): 664–685. doi:10.1016/j.ajhg.2017.09.008. PMC 5673604. PMID 29100083.
  56. ^ Ishii A, Kang JQ, Schornak CC, Hernandez CC, Shen W, Watkins JC, et al. (March 2017). "A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy". Journal of Medical Genetics. 54 (3): 202–211. doi:10.1136/jmedgenet-2016-104083. PMC 5384423. PMID 27789573.
  57. ^ May P, Girard S, Harrer M, Bobbili DR, Schubert J, Wolking S, et al. (August 2018). "Rare coding variants in genes encoding GABAA receptors in genetic generalised epilepsies: an exome-based case-control study". The Lancet. Neurology. 17 (8): 699–708. doi:10.1016/S1474-4422(18)30215-1. hdl:10138/309565. PMID 30033060. S2CID 51710179.
  58. ^ Bosch DG, Boonstra FN, de Leeuw N, Pfundt R, Nillesen WM, de Ligt J, et al. (May 2016). "Novel genetic causes for cerebral visual impairment". European Journal of Human Genetics. 24 (5): 660–5. doi:10.1038/ejhg.2015.186. PMC 4930090. PMID 26350515.
  59. ^ Srivastava S, Cohen J, Pevsner J, Aradhya S, McKnight D, Butler E, et al. (November 2014). "A novel variant in GABRB2 associated with intellectual disability and epilepsy". American Journal of Medical Genetics. Part A. 164A (11): 2914–21. doi:10.1002/ajmg.a.36714. PMC 4205182. PMID 25124326.
  60. ^ Kumari R, Lakhan R, Kalita J, Garg RK, Misra UK, Mittal B (June 2011). "Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population". Clinica Chimica Acta; International Journal of Clinical Chemistry. 412 (13–14): 1244–8. doi:10.1016/j.cca.2011.03.018. PMID 21420396.
  61. ^ Blatt GJ, Fitzgerald CM, Guptill JT, Booker AB, Kemper TL, Bauman ML (December 2001). "Density and distribution of hippocampal neurotransmitter receptors in autism: an autoradiographic study". Journal of Autism and Developmental Disorders. 31 (6): 537–43. doi:10.1023/a:1013238809666. PMID 11814263. S2CID 22347772.
  62. ^ Ma DQ, Whitehead PL, Menold MM, Martin ER, Ashley-Koch AE, Mei H, et al. (September 2005). "Identification of significant association and gene-gene interaction of GABA receptor subunit genes in autism". American Journal of Human Genetics. 77 (3): 377–88. doi:10.1086/433195. PMC 1226204. PMID 16080114.
  63. ^ Cogliati F, Giorgini V, Masciadri M, Bonati MT, Marchi M, Cracco I, et al. (July 2019). "Pathogenic Variants in STXBP1 and in Genes for GABAa Receptor Subunities Cause Atypical Rett/Rett-like Phenotypes". International Journal of Molecular Sciences. 20 (15): 3621. doi:10.3390/ijms20153621. PMC 6696386. PMID 31344879.
  64. ^ Sajan SA, Jhangiani SN, Muzny DM, Gibbs RA, Lupski JR, Glaze DG, et al. (January 2017). "Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2". Genetics in Medicine. 19 (1): 13–19. doi:10.1038/gim.2016.42. PMC 5107176. PMID 27171548.
  65. ^ Chen CY, Di Lucente J, Lin YC, Lien CC, Rogawski MA, Maezawa I, et al. (January 2018). "Defective GABAergic neurotransmission in the nucleus tractus solitarius in Mecp2-null mice, a model of Rett syndrome". Neurobiology of Disease. 109 (Pt A): 25–32. doi:10.1016/j.nbd.2017.09.006. PMC 5696074. PMID 28927958.
  66. ^ Li Y, Sun H, Chen Z, Xu H, Bu G, Zheng H (23 February 2016). "Implications of GABAergic Neurotransmission in Alzheimer's Disease". Frontiers in Aging Neuroscience. 8: 31. doi:10.3389/fnagi.2016.00031. PMC 4763334. PMID 26941642.
  67. ^ Li JQ, Yuan XZ, Li HY, Cao XP, Yu JT, Tan L, et al. (May 2018). "Genome-wide association study identifies two loci influencing plasma neurofilament light levels". BMC Medical Genomics. 11 (1): 47. doi:10.1186/s12920-018-0364-8. PMC 5946407. PMID 29747637.
  68. ^ Jiang S, Wen N, Li Z, Dube U, Del Aguila J, Budde J, et al. (December 2018). "Integrative system biology analyses of CRISPR-edited iPSC-derived neurons and human brains reveal deficiencies of presynaptic signaling in FTLD and PSP". Translational Psychiatry. 8 (1): 265. doi:10.1038/s41398-018-0319-z. PMC 6293323. PMID 30546007.
  69. ^ Matarin M, Salih DA, Yasvoina M, Cummings DM, Guelfi S, Liu W, et al. (February 2015). "A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology". Cell Reports. 10 (4): 633–44. doi:10.1016/j.celrep.2014.12.041. hdl:11336/51730. PMID 25620700.
  70. ^ Wiseman SM, Haddad Z, Walker B, Vergara IA, Sierocinski T, Crisan A, et al. (October 2013). "Whole-transcriptome profiling of thyroid nodules identifies expression-based signatures for accurate thyroid cancer diagnosis". The Journal of Clinical Endocrinology and Metabolism. 98 (10): 4072–9. doi:10.1210/jc.2013-1991. PMID 23928671.
  71. ^ Alexander EK, Kennedy GC, Baloch ZW, Cibas ES, Chudova D, Diggans J, et al. (August 2012). "Preoperative diagnosis of benign thyroid nodules with indeterminate cytology". The New England Journal of Medicine. 367 (8): 705–15. doi:10.1056/NEJMoa1203208. PMID 22731672. S2CID 4992970.
  72. ^ Barros-Filho MC, Marchi FA, Pinto CA, Rogatto SR, Kowalski LP (June 2015). "High Diagnostic Accuracy Based on CLDN10, HMGA2, and LAMB3 Transcripts in Papillary Thyroid Carcinoma". The Journal of Clinical Endocrinology and Metabolism. 100 (6): E890-9. doi:10.1210/jc.2014-4053. hdl:11449/164900. PMID 25867809.
  73. ^ Wang QX, Chen ED, Cai YF, Li Q, Jin YX, Jin WX, et al. (October 2016). "A panel of four genes accurately differentiates benign from malignant thyroid nodules". Journal of Experimental & Clinical Cancer Research. 35 (1): 169. doi:10.1186/s13046-016-0447-3. PMC 5084448. PMID 27793213.
  74. ^ Beltrami CM, Dos Reis MB, Barros-Filho MC, Marchi FA, Kuasne H, Pinto CA, et al. (December 2017). "Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas". Clinical Epigenetics. 9 (1): 45. doi:10.1186/s13148-017-0346-2. PMC 5414166. PMID 28469731.
  75. ^ Jin Y, Jin W, Zheng Z, Chen E, Wang Q, Wang Y, et al. (October 2017). "GABRB2 plays an important role in the lymph node metastasis of papillary thyroid cancer". Biochemical and Biophysical Research Communications. 492 (3): 323–330. doi:10.1016/j.bbrc.2017.08.114. PMID 28859983.
  76. ^ Knott EL, Leidenheimer NJ (November 2020). "A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression". International Journal of Molecular Sciences. 21 (22): 8485. doi:10.3390/ijms21228485. PMC 7697095. PMID 33187258.
  77. ^ Chen W, Liu BY, Zhang X, Zhao XG, Cao G, Dong Z, et al. (August 2016). "Identification of differentially expressed genes in salivary adenoid cystic carcinoma cells associated with metastasis". Archives of Medical Science. 12 (4): 881–8. doi:10.5114/aoms.2016.60973. PMC 4947631. PMID 27478471.
  78. ^ Gross AM, Kreisberg JF, Ideker T (10 November 2015). "Analysis of Matched Tumor and Normal Profiles Reveals Common Transcriptional and Epigenetic Signals Shared across Cancer Types". PLOS ONE. 10 (11): e0142618. Bibcode:2015PLoSO..1042618G. doi:10.1371/journal.pone.0142618. PMC 4640835. PMID 26555223.
  79. ^ Liu A, Zhao H, Sun B, Han X, Zhou D, Cui Z, et al. (March 2020). "A predictive analysis approach for paediatric and adult high-grade glioma: miRNAs and network insight". Annals of Translational Medicine. 8 (5): 242. doi:10.21037/atm.2020.01.12. PMC 7154480. PMID 32309389.
  80. ^ Liu BX, Huang GJ, Cheng HB (November 2019). "Comprehensive Analysis of Core Genes and Potential Mechanisms in Rectal Cancer". Journal of Computational Biology. 26 (11): 1262–1277. doi:10.1089/cmb.2019.0073. PMID 31211595. S2CID 195066103.
  81. ^ Markert JM, Fuller CM, Gillespie GY, Bubien JK, McLean LA, Hong RL, et al. (February 2001). "Differential gene expression profiling in human brain tumors". Physiological Genomics. 5 (1): 21–33. doi:10.1152/physiolgenomics.2001.5.1.21. PMID 11161003. S2CID 89526.
  82. ^ Narasimhan K, Gauthaman K, Pushparaj PN, Meenakumari G, Chaudhary AG, Abuzenadah A, et al. (22 April 2014). "Identification of Unique miRNA Biomarkers in Colorectal Adenoma and Carcinoma Using Microarray: Evaluation of Their Putative Role in Disease Progression". ISRN Cell Biology. 2014: 1–10. doi:10.1155/2014/526075.
  83. ^ Yan L, Gong YZ, Shao MN, Ruan GT, Xie HL, Liao XW, et al. (July 2020). "Distinct diagnostic and prognostic values of γ-aminobutyric acid type A receptor family genes in patients with colon adenocarcinoma". Oncology Letters. 20 (1): 275–291. doi:10.3892/ol.2020.11573. PMC 7286117. PMID 32565954.
  84. ^ Hartiadi LY, Ahring PK, Chebib M, Absalom NL (March 2016). "High and low GABA sensitivity α4β2δ GABAA receptors are expressed in Xenopus laevis oocytes with divergent stoichiometries". Biochemical Pharmacology. 103: 98–108. doi:10.1016/j.bcp.2015.12.021. PMID 26774457.
  85. ^ Laha KT, Tran PN (January 2013). "Multiple tyrosine residues at the GABA binding pocket influence surface expression and mediate kinetics of the GABAA receptor". Journal of Neurochemistry. 124 (2): 200–9. doi:10.1111/jnc.12083. PMC 3535540. PMID 23121119.
  86. ^ Tierney ML, Luu T, Gage PW (January 2008). "Functional asymmetry of the conserved cystine loops in alphabetagamma GABA A receptors revealed by the response to GABA activation and drug potentiation". The International Journal of Biochemistry & Cell Biology. 40 (5): 968–79. doi:10.1016/j.biocel.2007.10.029. hdl:1885/32939. PMID 18083058. S2CID 85243629.
  87. ^ Cirone J, Rosahl TW, Reynolds DS, Newman RJ, O'Meara GF, Hutson PH, et al. (June 2004). "Gamma-aminobutyric acid type A receptor beta 2 subunit mediates the hypothermic effect of etomidate in mice". Anesthesiology. 100 (6): 1438–45. doi:10.1097/00000542-200406000-00016. PMID 15166563. S2CID 56938370.
  88. ^ Groves JO, Guscott MR, Hallett DJ, Rosahl TW, Pike A, Davies A, et al. (July 2006). "The role of GABAbeta2 subunit-containing receptors in mediating the anticonvulsant and sedative effects of loreclezole". The European Journal of Neuroscience. 24 (1): 167–74. doi:10.1111/j.1460-9568.2006.04890.x. PMID 16882014. S2CID 25219171.
  89. ^ Baur R, Kielar M, Richter L, Ernst M, Ecker GF, Sigel E (July 2013). "Molecular analysis of the site for 2-arachidonylglycerol (2-AG) on the β₂ subunit of GABA(A) receptors". Journal of Neurochemistry. 126 (1): 29–36. doi:10.1111/jnc.12270. PMID 23600744. S2CID 45338392.
  90. ^ Li X, Yang Q, Hu Y (January 2006). "Regulation of the expression of GABAA receptor subunits by an antiepileptic drug QYS". Neuroscience Letters. 392 (1–2): 145–9. doi:10.1016/j.neulet.2005.09.011. PMID 16214289. S2CID 45399504.
  91. ^ Zhang Y, Mayer-Blackwell B, Schlussman SD, Randesi M, Butelman ER, Ho A, et al. (April 2014). "Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6 J mice". Psychopharmacology. 231 (7): 1277–87. doi:10.1007/s00213-013-3306-3. PMC 3954898. PMID 24221825.
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