No association of GABRA1 rs2279020 and GABRA6 rs3219151 polymorphisms with risk of epilepsy and antiepileptic drug responsiveness in Asian and Arabic populations: Evidence from a meta-analysis with trial sequential analysis

Abstract

The γ-aminobutyric acid type A receptors (GABAAR) have been reported to contribute to the pathogenesis of epilepsy and the recurrence of chronic seizures. Genetic polymorphisms in GABRA1 and GABRA6 may confer a high risk of epilepsy and multiple drug resistance, but with conflicting results. We aimed to assess the association of GABRA1 rs2279020 and GABRA6 rs3219151 with epilepsy risk using a meta-analysis. The databases of Pubmed, Ovid, Web of Science, and China National Knowledge Infrastructure were searched. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed to evaluate the association between the polymorphisms and epilepsy risk using a fixed- or random-effect model. Trial sequential analysis (TSA) was performed to assess the results of the meta-analysis. No significant association between the GABRA1 rs2279020 and GABRA6 rs3219151 and the risk of epilepsy was found in the Asian and Arabic populations. The negative results were also observed when comparing the GABRA1 rs2279020 and GABRA6 rs3219151 polymorphism to antiepileptic drug responsiveness. The trial sequential analysis confirmed the results of the meta-analysis. This meta-analysis suggests that GABRA1 rs2279020 and GABRA6 rs3219151 are not risk factors for the etiology of epilepsy and antiepileptic drug responsiveness in the Asian and Arabic populations.

Association between Genetic Polymorphism of SCN1A, GABRA1 and ABCB1 and Drug Responsiveness in Vietnamese Epileptic Children

“…Similarly, in Indian patients, both the GG genotype and G allele were demonstrated as risk factors of multiple drug resistance [35]. On the contrary, there was no association of GABRA1 rs2279020 with predisposition of AEDs resistance in Asian and Arabic populations [37,38]. The ABCB1 gene encodes P-glycoprotein and the efflux transporter that modulates antiepileptic drug pharmacokinetics through the absorption process in the intestine and brain penetrance.…”

Population structure and selection signal analysis of indigenous sheep from the southern edge of the Taklamakan Desert

“…Loss or mutations in TBL1XR1 can lead to abnormal motor coordination. GABRA1 and GABRA6 , exclusive to the nervous system, regulate brain development mechanisms [ 76 , 77 ], and reduced levels may compromise motor function. GRID2 , expressed in layer V cortical neurons involved in motor function formation, underpins motor control and limb coordination.…”

The Polypharmacological Effects of Cannabidiol

“…The modulation of ionic currents of ion channels such as GABA A R [ 41 ], Nav [ 71 , 72 ], and less documented Cav [ 75 ] might be important in the anticonvulsant and antiepileptic effect of CBD. First, the combined effect of CBD with clobazam (CBD acts as PAM on GABA A R) [ 41 ] has an important role in the suppression of common epileptic events by maintaining homeostasis over brain excitation and its importance for treating drug-resistant epilepsy caused by mutations that alter the channel [ 170 ]. Secondly, the target of CBD to treat DS is the non-specific inhibitory effect on the mutated sodium channels Nav 1.1 and Nav 1.2 [ 73 , 74 ]; although, it is also capable of inhibiting other sodium channels such as Nav1.3, Nav1.4, Nav1.5, Nav1.6, and Nav1.7 [ 71 , 72 ].…”