Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required.
Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required.
The alpha1/beta2/gamma2-containing heteropentamer is the most abundant gamma-amino-n-butyric acid type A receptor subtype in mammalian brains and the corresponding genes, the GABRA1, GABRB2, and GABRG2 genes, are located in chromosomal region 5q34 that several genome wide scans have implicated as a susceptibility region for schizophrenia.
A GABA(A) receptor gene cluster on 5q31-35 (beta2 [GABRB2], alpha6 [GABRA6], alpha1 [GABRA1], and gamma2 [GABRG2] subunit genes) is one of the most attractive candidate regions for schizophrenia susceptibility.
We performed 1) systematic polymorphism search of GABRB2, GABRA6, and GABRA1, in addition to our colleague's study of GABRG2; 2) evaluation of linkage disequilibrium (LD) within this cluster with 35 single nucleotide polymorphisms (SNPs); 3) "selection of haplotype-tagging (ht) SNPs"; and 4) two-stage association analysis that comprised first-set screening analysis of all htSNPs (288 Japanese schizophrenia patients and 288 control subjects) and second-set replication analysis of the positive htSNPs (901 schizophrenic patients and 806 control subjects).
Although no associations were found in either allelic or genotypic frequencies, we detected a haplotypic association in GABRG2 with METH use disorder, but not with schizophrenia.