Anti-GABRA5 (aa 360-409) polyclonal antibody

Aim: We aimed to identify the effect of SNPs in the -subunits of GABA(A) receptors on epilepsy treatment outcomes by using a gene-wide tagging method. Materials & methods: There were 720 epileptic patients included in the present study. A total of 136 tagging SNPs in GABRA1, GABRA2, GABRA3, GABRA4, GABRA5 and GABRA6 were genotyped by Illumina((R))GoldenGate((R)) Genotyping platform. Clinical information, such as prescribed antiepileptic drugs, height, weight, epilepsy syndrome classification, etiology, number of attacks, renal function and liver function were collected. The associations between SNPs and epilepsy treatment outcomes were analyzed using SAS((R)) version 9.1.3. Both multivariate logistic regression and multifactor dimensionality reduction analyses were performed. Results: The results of single gene effects did not remain significant after Bonferroni's corrections. Further multivariate logistic regression and multifactor dimensionality reduction analyses of interactions between these genes showed that under adjustment of clinical factors, the epilepsy treatment outcomes were significantly associated with the genotype combinations of GABRA1 rs6883877, GABRA2 rs511310 and GABRA3 rs4828696 (p < 0.0001; adjusted r(2) = 0.149). Conclusion: Our results indicated that genetic variants in the subunits of GABA(A) receptors may interactively affect the treatment responses of antiepileptic drugs. Further replication using an independent sample collection would be essential to confirm our findings. Original submitted 13 June 2013; Revision submitted 12 August 2013

BackgroundEthanol (EtOH) affects the immune system. Binge drinking of hard liquor initiates a stress response. This form of drinking is popular during adolescence, which involves maturation of the immune system. The spleen is a key immune organ, and spleen atrophy is associated with immunosuppression. While the hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the initial stress response, the hippocampus may be involved in stress beyond the HPA axis. MethodsBlood ethanol concentration (BEC), blood endotoxin levels, and plasma corticosterone levels were measured following binge EtOH treatment. Absolute and relative spleen sizes were analyzed, and stress-related gene expression was compared in the hypothalamus and hippocampus. Polymerase chain reaction array was performed to analyze the expression profile of EtOH metabolism and immune regulation-related genes in the spleen. Relationships among variables were analyzed using the Pearson correlation. ResultsAt 24hours following a 3-day EtOH treatment, no significant difference in BEC was detected between EtOH-treated and control rats. Average plasma endotoxin levels in EtOH-treated animals were significantly higher than in controls, and spleen size was significantly lower. Spleen size did not correlate with plasma endotoxin levels; however, it did significantly negatively correlate with plasma corticosterone levels. Spleen size significantly negatively correlated with hippocampal CRH expression and significantly positively correlated with hippocampal MR expression. No correlation was observed in the hypothalamus. Significantly higher hippocampal CRH and significantly lower MR expression was seen in low spleen/body weight (sp-wt) ratio rats. No gene was found to decrease expression 1.5-fold (p<0.05) in the spleen of high sp-wt group, whereas expression of several genes, including Gabra1,Gabra5,Ifnb1,Irf9,Il12b, and Cx3cr1, decreased significantly in the low sp-wt group. ConclusionsOur findings suggest that binge EtOH exposure causes lower spleen size in adolescents and that the hippocampus and stress may be associated with alterations in spleen structure and gene expression.