No interaction of GABAA alpha-1 subunit and dopamine receptor D4 exon 3 genes in symptomatology of major psychoses

Abstract

Previously, we reported on an association of the dopamine receptor D4 (DRD4) gene with delusional symptomatology of major psychoses. However, despite the strength of the association, it only accounted for 2% of the variance, indicating that contributions from other genes were probable. In the present study, we investigated the original cohort of subjects to evaluate the gene for the gamma-aminobutyric acid type A (GABA(A)) receptor alpha-1 subunit (GABRA1). The possible association of GABRA1 with the psychopathology of major psychoses was tested both alone and in interaction with DRD4. Four hundred and sixty-one inpatients affected by major psychoses were assessed by the operational criteria checklist for psychotic illness (OPCRIT) and were also typed for the DRD4 and GABRA1 variants using PCR techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. GABRA1 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects such as sex and psychiatric diagnosis also did not reveal any association. GABRA1 variants did not significantly influence the association of DRD4 with delusional symptoms. No interaction was observed on the other symptom factors. The GABA(A) alpha-1 subunit gene does not, therefore, interact with DRD4 in the symptomatology of major psychoses.

The α1 subunit of the γ-aminobutyric acid receptor, Gabra1, is differentially expressed in the brains of patients with schizophrenia.

“…We identified four separate studies investigating relationships between psychotic disorders and GABRA1. One study concluded that variants in the GABRA1 gene were not significantly associated with mania, depression, delusion or disorganization, and that there was no interaction between GABRA1 and the D4 dopamine receptor, for which a positive association with delusional symptomology had previously been established 15 . However, a separate study found that in a Portuguese patient population, haplotypes Hap9A and Hap10A were found in excess in patients as compared to controls; haplotype blocks 9 and 10 contain all schizophreniaassociated single nucleotide polymorphisms (SNP) 16 .…”

Mutational screening and association study of glutamate decarboxylase 1 as a candidate susceptibility gene for bipolar affective disorder and schizophrenia

“…The focus of molecular genetic studies of the GABAergic system in BPAD and schizophrenia has so far been on simple repeat markers in GABA-A receptor (GABRA) subunit genes including: GABRAa1-6 [Coon et al, 1994;Oruc et al, 1997;Papadimitriou et al, 1998Papadimitriou et al, , 2001aSerretti et al, 1998Serretti et al, , 1999Duffy et al, 2000], GABRAb1 [Coon et al, 1994;Puertollano et al, 1997], GABRAb3 [Puertollano et al, 1995;Oruc et al, 1996;Duffy et al, 2000;Papadimitriou et al, 2001b], and GABRAg2 [Coon et al, 1994]. Significant association has been reported between GABRAa5 markers and BPAD [Papadimitriou et al, 1998], unipolar disorder [Oruc et al, 1997], late onset (>25 years) schizophrenia [Papadimitriou et al, 2001a], and recently between a GABRAa3 marker and BPAD [Massat et al, 2002].…”

NOS‐I and ‐III gene variants are differentially associated with facets of suicidal behavior and aggression‐related traits

“…Genotypes were analyzed avoiding the a priori dominance specification according to literature standards and using dummy variables (i.e., presence/absence of each genotype) and their combination (e.g. NOS‐I rs693534 G/G = 1, A/G = 2 plus NOS‐III rs891512 G/G = 1, A/G = 2) being the third genotype redundant [Kühn et al, 1999; Serretti et al, 1999; Lerer et al, 2001].…”