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Gene Review:

GABRA2 - gamma-aminobutyric acid (GABA) A receptor,...

Homo sapiens

Synonyms: GABA(A) receptor subunit alpha-2, Gamma-aminobutyric acid receptor subunit alpha-2

Edenberg, H.J. et al., Dick, D.M. et al., Higuchi, S. et al., Fehr, C. et al., Drgon, T. et al., et al.

Lappalainen, Krupitsky, Remizov, Pchelina, Taraskina, Zvartau, Somberg, Covault, Kranzler, Krystal, Gelernter, Fehr, Sander, Tadic, Lenzen, Anghelescu, Klawe, Dahmen, Schmidt, Szegedi, Dick, Agrawal, Schuckit, Bierut, Hinrichs, Fox, Mullaney, Cloninger, Hesselbrock, Nurnberger, Almasy, Foroud, Porjesz, Edenberg, Begleiter, Dick, Bierut, Hinrichs, Fox, Bucholz, Kramer, Kuperman, Hesselbrock, Schuckit, Almasy, Tischfield, Porjesz, Begleiter, Nurnberger, Xuei, Edenberg, Foroud,

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Psychiatry related information on GABRA2

In a sample of children and adolescents ascertained as part of the COGA project, we find that GABRA2 is significantly associated with childhood conduct disorder symptoms, but not with childhood alcohol dependence symptoms [1].
GABRA2 is also associated with other drug dependence in our sample, both in adolescence and adulthood [1].

High impact information on GABRA2

Thirty-one SNPs in GABRA2, but only 1 of the 20 SNPs in the flanking genes, showed significant association with alcoholism [2].
The region of strongest association with alcohol dependence extended from intron 3 past the 3' end of GABRA2; all 43 of the consecutive three-SNP haplotypes in this region of GABRA2 were highly significant [2].
The very strong association of GABRA2 with both alcohol dependence and the beta frequency of the electroencephalogram, combined with biological evidence for a role of this gene in both phenotypes, suggest that GABRA2 might influence susceptibility to alcohol dependence by modulating the level of neural excitation [2].
To examine the moderating role of genetic variation in GABRA2, a single-nucleotide polymorphism that was informative in association studies was included as a factor in the analysis [3].
Alternative splicing and promoter use in the human GABRA2 gene [4].

Biological context of GABRA2

We use findings from the behavior genetics literature about how genetic factors (latently) influence alcohol dependence and related disorders to develop and test hypotheses about the risk associated with a specific gene, GABRA2, across different developmental stages [1].
The high-risk genotype at GABRA2 was also related to a decreased likelihood of marrying and an increased likelihood of divorce, which appeared to be mediated in part by personality characteristics [5].
These results delineate the haplotypes and patterns of linkage disequilibrium in this region, focus attention of the GABRA2 gene and identify modest associations between GABRA2 genotypes and addiction phenotypes [6].

Other interactions of GABRA2

(d) Examination of family-based samples has identified several genes including GABRA2 and CHRM2 thought to be associated with alcohol dependence [7].

Analytical, diagnostic and therapeutic context of GABRA2

Petersburg and genotyped for seven GABRA2 single-nucleotide polymorphisms (SNPs) using real-time PCR (TaqMan) [8].
RESULTS: The overall alcohol-dependent patients vs. control group comparison confirmed positive allelic association for five of six single-nucleotide polymorphisms mapping from intron 3 to the 3' end of GABRA2 (P=0.01-0.02) [9].

References

The role of GABRA2 in risk for conduct disorder and alcohol and drug dependence across developmental stages. Dick, D.M., Bierut, L., Hinrichs, A., Fox, L., Bucholz, K.K., Kramer, J., Kuperman, S., Hesselbrock, V., Schuckit, M., Almasy, L., Tischfield, J., Porjesz, B., Begleiter, H., Nurnberger, J., Xuei, X., Edenberg, H.J., Foroud, T. Behav. Genet. (2006) [Pubmed]
Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Edenberg, H.J., Dick, D.M., Xuei, X., Tian, H., Almasy, L., Bauer, L.O., Crowe, R.R., Goate, A., Hesselbrock, V., Jones, K., Kwon, J., Li, T.K., Nurnberger, J.I., O'Connor, S.J., Reich, T., Rice, J., Schuckit, M.A., Porjesz, B., Foroud, T., Begleiter, H. Am. J. Hum. Genet. (2004) [Pubmed]
GABRA2 alleles moderate the subjective effects of alcohol, which are attenuated by finasteride. Pierucci-Lagha, A., Covault, J., Feinn, R., Nellissery, M., Hernandez-Avila, C., Oncken, C., Morrow, A.L., Kranzler, H.R. Neuropsychopharmacology (2005) [Pubmed]
Alternative splicing and promoter use in the human GABRA2 gene. Tian, H., Chen, H.J., Cross, T.H., Edenberg, H.J. Brain Res. Mol. Brain Res. (2005) [Pubmed]
Marital status, alcohol dependence, and GABRA2: evidence for gene-environment correlation and interaction. Dick, D.M., Agrawal, A., Schuckit, M.A., Bierut, L., Hinrichs, A., Fox, L., Mullaney, J., Cloninger, C.R., Hesselbrock, V., Nurnberger, J.I., Almasy, L., Foroud, T., Porjesz, B., Edenberg, H., Begleiter, H. J. Stud. Alcohol (2006) [Pubmed]
Linkage disequilibrium, haplotype and association studies of a chromosome 4 GABA receptor gene cluster: Candidate gene variants for addictions. Drgon, T., D'Addario, C., Uhl, G.R. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2006) [Pubmed]
New findings on the genetic influences on alcohol use and dependence. Higuchi, S., Matsushita, S., Kashima, H. Current opinion in psychiatry. (2006) [Pubmed]
Association between alcoholism and gamma-amino butyric acid alpha2 receptor subtype in a Russian population. Lappalainen, J., Krupitsky, E., Remizov, M., Pchelina, S., Taraskina, A., Zvartau, E., Somberg, L.K., Covault, J., Kranzler, H.R., Krystal, J.H., Gelernter, J. Alcohol. Clin. Exp. Res. (2005) [Pubmed]
Confirmation of association of the GABRA2 gene with alcohol dependence by subtype-specific analysis. Fehr, C., Sander, T., Tadic, A., Lenzen, K.P., Anghelescu, I., Klawe, C., Dahmen, N., Schmidt, L.G., Szegedi, A. Psychiatr. Genet. (2006) [Pubmed]

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