Associations between CYP3A4, CYP3A5 and SCN1A polymorphisms and carbamazepine metabolism in epilepsy: A meta-analysis

Zhao, Gui-Xin; Zhang, Zheng; Cai, Wen-Ke; Shen, Ming-Li; Wang, Ping; He, Gong-Hao

doi:10.1016/j.eplepsyres.2021.106615

Cited by 9 publications

(10 citation statements)

References 64 publications

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“…Two studies have found a correlation between the A allele and combined genotypes GA + AA for SNV rs2298771 and the poor response to antiepileptic sodium channel blockers [ 19 , 22 ]. In contrast, five studies have found no association between genotypes from SNV rs2298771 and sodium channel blocker metabolism or resistance [ 20 , 21 , 23 , 24 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Seven studies have evaluated the susceptibility for general epilepsy seizure, multidrug resistance, and the SNV rs3812718 [ 19 , 20 , 22 , 23 , 26 , 27 , 28 ]. Only one study has analyzed TLE risk and the SNV rs3812718 [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Epileptic seizure susceptibility versus multidrug resistance has recently been related to the different genotypes from SNVs in the SCN1A gene, including SNV c.3184A>G (rs2298771) and SNV IVS5N+5G>A (rs3812718) [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. There is only one study that has evaluated the SNV rs3812718 and risk in relation to non-multidrug resistance in patients with TLE [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

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Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy—A Preliminary Study in a Brazilian Cohort Sample

Buainain,

Sodré,

dos Santos

et al. 2024

IJMS

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The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy–Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06–3.37); OR = 1.38 (95%CI = 1.04–1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25–5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01–2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08–5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04–17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy—A Preliminary Study in a Brazilian Cohort Sample

Buainain,

Sodré,

dos Santos

et al. 2024

IJMS

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“…A recent meta-analysis including eight studies reported that Asian patients with epilepsy and the GG genotype of the SCN1A-A3184G polymorphism are at a higher risk of carbamazepine resistance [36]. On the other hand, another meta-analysis including 18 studies (2546 patients) reported no association between the same polymorphism and the carbamazepine resistance [37]. Regarding the valproic acid, a Chinese study suggested that SCN1A-A3184G polymorphism has no effect on the drug response [38].…”

Section: Characteristicsmentioning

confidence: 99%

Polymorphisms of the sodium voltage-gated channel, alpha subunit 1 (SCN1A -A3184G) gene among children with non-lesional epilepsy: a case-control study

2022

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Background Mutations in the neuronal sodium voltage-gated channel, alpha subunit 1 (SCN1A) gene have been associated with epilepsy. We investigated the SCN1A-A3184G polymorphism among Egyptian children and adolescents with non-lesional epilepsy. Methods A prospective case – control observational study was done in Mansoura University Children’s Hospital, Egypt including 326 children with non-lesional epilepsy (163 antiepileptic drugs (AEDs) resistant cases & 163 AEDs responders) and 163 healthy controls. One step real time polymerase chain reaction (PCR) was used for the molecular analysis. Student’s t-test, and Monto Carlo, chi-square and Mann–Whitney tests were used for the statistical analysis. Results All study participants were matched as regards the age, sex and body weight (p = 0.07, 0.347 and 0.462, respectively). They had the (AA) and (AG) genotypes but not the (GG) variant. No significant differences were found between cases and controls regarding (AG) and (AA) genotypes and A- and G-alleles (p = 0.09 and 0.3, respectively). We did not find significant differences between AEDs responders and resistant cases regarding the studied genotypes and alleles (p = 0.61 and 0.746, respectively). In the resistant group, we observed significant associations between the (AG) genotype and seizure frequency (p = 0.05), the tonic-clonic seizure (p < 0.001), the younger age of first seizure attack (p = 0.03), abnormal electroencephalogram (EEG) (p < 0.001), the positive family history of epilepsy (p = 0.006), topiramate (p = 0.03) and valproic acid (p < 0.001), while the (AA) genotype was associated with carbamazepine (p = 0.03). While in AEDs responders, there were significant associations between the AG genotype and the abnormal EEG activity, levetiracetam and carbamazepine (p = 0.016, 0.028 and 0.02). Conclusions The SCN1A-A3184G genotypes and alleles were not associated with the epilepsy risk among Egyptian children. Significant associations were reported between the AG genotype and some predictors of refractory epilepsy.

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“…Subsequently, CBZE was hydrolyzed by microsomal epoxide hydrolase to the inactive metabolite carbamazepine-10,11-trans dihydrodiol. Only 1% of carbamazepine was excreted from urine in its original form, and its half-life is about 15 h ( 36 , 37 ). Its molecular weight is 236, protein binding rate is 74%, and distribution volume is 0.8–1.8 L/kg ( 20 ).…”

Section: Metabolic Pathway Of Asms and The Influence Of Asms In Human...mentioning

confidence: 99%

Management of anti-seizure medications in lactating women with epilepsy

et al. 2022

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Epilepsy is a common neurological disease. At present, there are about 70 million epilepsy patients in the world, half of them are women, and 30–40% of women with epilepsy are of childbearing potential. Patients with epilepsy who are of childbearing potential face more challenges, such as seizures caused by hormonal fluctuations and the risk of adverse effects on the mother and baby from taking anti-seizure medications (ASMs). Breast milk is one of the best gifts that a mother can give her baby, and breastfeeding can bring more benefits to the baby. Compared with healthy people, people with epilepsy have more concerns about breastfeeding because they are worried that ASMs in their milk will affect the growth and development of the baby, and they are always faced with the dilemma of whether to breastfeed after childbirth. Regarding, whether women with epilepsy can breastfeed while taking ASMs, and whether breastfeeding will adversely affect the baby is still an important topic of concern for patients and doctors. This article reviews the existing research on breastfeeding-related issues in women with epilepsy to guide clinical practice, and improve the breastfeeding compliance of women with epilepsy.

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Associations between CYP3A4, CYP3A5 and SCN1A polymorphisms and carbamazepine metabolism in epilepsy: A meta-analysis

Cited by 9 publications

References 64 publications

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy—A Preliminary Study in a Brazilian Cohort Sample

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy—A Preliminary Study in a Brazilian Cohort Sample

Polymorphisms of the sodium voltage-gated channel, alpha subunit 1 (SCN1A -A3184G) gene among children with non-lesional epilepsy: a case-control study

Management of anti-seizure medications in lactating women with epilepsy

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