Impact of GABAA receptor gene variants (rs2279020 and rs211037) on the risk of predisposition to epilepsy: a case–control study

Amjad, Maryam; Tabassum, Asma; Sher, Khalid; Kumar, Suneel; Zehra, Sitwat; Fatima, Sehrish

doi:10.1007/s10072-022-05947-7

Cited by 2 publications

(3 citation statements)

References 35 publications

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“…Previously, an SNP located in intron 10 of GABRA1 (rs2279020) was reported to be potentially functional, with the A→ G shift changing the shape of the protein that led to alternative splicing (32). A significant association of the rs2279020 with epilepsy risk was reported by some research groups (16, 26, 32), whereas no significant association was reported by other research groups (13,17,23,25). The controversial results were also observed in comparison to the rs2279020 with AED resistance (16,17,24,25).…”

Section: Discussionmentioning

confidence: 99%

“…In human and animal studies, the differential expression and composition of GABA A Rs subunits may contribute to the pathogenesis of epilepsy and the recurrence of chronic seizures ( 12 ). Single nucleotide polymorphisms (SNP) in any of the subunits may alter the expression of GABA, and ultimately influence epilepsy seizures and responsiveness to AEDs ( 13 – 15 ). For example, Kumari et al reported that the rs2279020 G allele in GABRA1 conferred a high risk of epilepsy and multiple drug resistance ( 16 ), whereas Al-Eitan et al reported that the rs2279020 polymorphism did not show any linkage with the occurrence of epilepsy and treatment responsiveness ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Yang²,

Sima

2022

Front. Neurol.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Yang²,

Sima

2022

Front. Neurol.

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“…GABRG2 variants may alter the expression of subunits of GABA A receptors (the mechanism is unclear), which may affect transcription, mRNA stability, and translation efficiency, leading to variations in receptor composition and its sensitivity to exogenous environmental signals (Abou El Ella et al, 2018). rs211037 is a synonymous SNP of the γ-2 subunit of the GABA A receptor (Amjad et al, 2022). Some studies have shown that the GABRG2 gene may be correlated with both epilepsy and drug-resistant epilepsy and so we conducted some meta-analyses of GABRG2 rs211037.…”

Section: Figure 11mentioning

confidence: 99%

Association between the SLC6A11 rs2304725 and GABRG2 rs211037 polymorphisms and drug-resistant epilepsy: a meta-analysis

Zhao

Yang

et al. 2023

Front. Physiol.

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Background: Previous studies have shown that SLC6A11 and GABRG2 are linked to drug-resistant epilepsy (DRE), although there have been conflicting results in the literature. In this study, we systematically assessed the relationship between DRE and these two genes.Methods: We systematically searched the PubMed, Embase, Cochrane Library, Web of Science, Google Scholar, Wanfang Data, CNKI, and VIP databases. To clarify whether heterogeneity existed between studies, tools such as the Q-test and I2 statistic were selected. According to study heterogeneity, we chose fixed- or random-effects models for analysis. We then used the chi-squared ratio to evaluate any bias of the experimental data.Results: In total, 11 trials and 3,813 patients were selected. To investigate the relationship with DRE, we performed model tests on the two genes separately. The results showed that SLC6A11 rs2304725 had no significant correlation with DRE risk in the allele, dominant, recessive, and additive models in a pooled population. However, for the over-dominant model, DRE was correlated with rs2304725 (OR = 1.08, 95% CI: 0.92–1.27, p = 0.33) in a pooled population. Similarly, rs211037 was weakly significantly correlated with DRE for the dominant, recessive, over-dominant, and additive models in a pooled population. The subgroup analysis results showed that rs211037 expressed a genetic risk of DRE in allele (OR = 1.01, 95% CI: 0.76–1.35, p = 0.94), dominant (OR = 1.08, 95% CI: 0.77–1.50, p = 0.65), and additive models (OR = 1.14, 95% CI: 0.62–2.09, p = 0.67) in an Asian population.Conclusion: In this meta-analysis, our results showed that SLC6A11 rs2304725 and GABRG2 rs211037 are not significantly correlated with DRE. However, in the over-dominant model, rs2304725 was significantly correlated with DRE. Likewise, rs211037 conveyed a genetic risk for DRE in an Asian population in the allele, dominant, and additive models.

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Impact of GABAA receptor gene variants (rs2279020 and rs211037) on the risk of predisposition to epilepsy: a case–control study

Cited by 2 publications

References 35 publications

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

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

Association between the SLC6A11 rs2304725 and GABRG2 rs211037 polymorphisms and drug-resistant epilepsy: a meta-analysis

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