Genetic Polymorphism of GABRG2 rs211037 is Associated with Drug Response and Adverse Drug Reactions to Valproic Acid in Chinese Southern Children with Epilepsy

Lu, Jieluan; Xia, Han-Bing; Li, Wenzhou; Shen, Xianhuan; Guo, Huijuan; Zhang, Jianping; Fan, Xiaomei

doi:10.2147/pgpm.s329594

Cited by 6 publications

(1 citation statement)

References 44 publications

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“…Patients were classified as persistent seizure when VPA monotherapy or therapy combined with other ASMs for at least 12 months failed to achieve sustained seizure freedom at the maximal tolerated dose. Patients were considered seizure-free if they did not experience any type of seizure during VPA treatment for at least 1 year [56,57]. The evaluation of VPA responsiveness was performed after a stable dose of VPA had been reached [58].…”

Section: Drug Response and Adrs Evaluationmentioning

confidence: 99%

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy

Zhu,

Lu,

et al. 2023

Pharmaceuticals

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Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

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Section: Drug Response and Adrs Evaluationmentioning

confidence: 99%

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy

Zhu,

Lu,

et al. 2023

Pharmaceuticals

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Association between GABRG2 Gene Single Nucleotide Polymorphisms and Susceptibility to Ischemic Stroke in a Chinese Population

Ma,

Zhao,

Xie

et al. 2023

J. Integr. Neurosci.

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Background: Current evidence suggests that Gamma-aminobutyric acid (GABA) receptors are associated with the occurrence and progression of cerebrovascular diseases. The present study investigated the association between single nucleotide polymorphisms (SNPs) in the Gamma-aminobutyric acid type A receptor gamma2 subunit (GABRG2) gene and ischemic stroke (IS). Methods: A total of 120 healthy volunteers and 187 patients with IS were recruited. Patients underwent complete neurological assessment and classification with the National Institute of Health Stroke Scale (NIHSS) and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze SNP sites in 4 different regions (rs211037, rs418210, rs211035, and rs424740) of the GABRG2 gene. SHEsis online platform was used to assess SNP allele and genotype frequencies. Multivariate logistic regression analysis was performed to identify the risk factors for IS. Results: Univariate analysis showed that the T allele and TT genotype distribution for rs211037 were significantly more frequent in the IS group compared to controls (pallele = 0.01, odds ratio (OR) = 1.673, 95% confidence intervals (CI), 1.119–2.500, pgenotype = 0.03). Furthermore, multivariate logistic regression analysis revealed the TT genotype for rs211037 was an independent risk factor for IS (p = 0.017, OR = 1.925, 95% CI, 1.122–3.303). Age was also found to be an independent risk factor, and the older the age, the higher the risk of IS (p = 0.001, OR = 1.047, 95% CI, 1.020–1.073). Finally, subgroup analysis revealed that patients with the rs211037 TT genotype were associated with a higher NIHSS score (p = 0.03), and that large-artery atherosclerosis (LAA) subtype was predominant in patients with the rs211037 TT genotype (p = 0.042). Conclusions: These findings suggest the rs211037 polymorphism in the GABRG2 gene is an independent risk factor for IS in the Chinese population. GABRG2 could thus be a potential biomarker to assess the risk of IS.

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Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets

Lin,

Ho,

Chen

et al. 2024

Front. Pharmacol.

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Antiseizure medications (ASMs) play a central role in seizure management, however, unpredictability in the response to treatment persists, even among patients with similar seizure manifestations and clinical backgrounds. An objective biomarker capable of reliably predicting the response to ASMs would profoundly impact epilepsy treatment. Presently, clinicians rely on a trial-and-error approach when selecting ASMs, a time-consuming process that can result in delays in receiving alternative non-pharmacological therapies such as a ketogenetic diet, epilepsy surgery, and neuromodulation therapies. Pharmacogenetic studies investigating the correlation between ASMs and genetic variants regarding their mechanistic targets offer promise in predicting the response to treatment. Sodium channel subunit genes have been extensively studied along with other ion channels and receptors as targets, however, the results have been conflicting, possibly due to methodological disparities including inconsistent definitions of drug response, variations in ASM combinations, and diversity of genetic variants/genes studied. Nonetheless, these studies underscore the potential effect of genetic variants on the mechanism of ASMs and consequently the prediction of treatment response. Recent advances in sequencing technology have led to the generation of large genetic datasets, which may be able to enhance the predictive accuracy of the response to ASMs.

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Genetic Polymorphism of GABRG2 rs211037 is Associated with Drug Response and Adverse Drug Reactions to Valproic Acid in Chinese Southern Children with Epilepsy

Cited by 6 publications

References 44 publications

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy

Association between GABRG2 Gene Single Nucleotide Polymorphisms and Susceptibility to Ischemic Stroke in a Chinese Population

Review of pharmacogenetics of antiseizure medications: focusing on genetic variants of mechanistic targets

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