Dataset Information

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

ABSTRACT:

Background

Previous studies have shown that the rs717620 polymorphism in ABCC2, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear.

Aims

The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms.

Main

methods: We conducted a literature search of five electronic databases, Embase, Medline, Web of Science, China National Knowledge Infrastructure, and Wanfang, to identify relevant studies on response to ASM therapy among rs717620 genotypes. Expression quantitative trait loci analysis and drug-gene interaction analysis were also performed to assess the underlying mechanisms.

Key findings

The pooled results for 18 studies revealed a significant association between rs717620 genotype and ASM resistance under the recessive model (TT vs. CT + CC: OR = 1.68, 95 % CI = 1.27-2.21, I² = 3.1 %). A significant association was also found in the Asian population under the recessive model (TT vs. CT + CC: OR = 1.70, 95 % CI = 1.26-2.29, I² = 29.3 %). Further analysis revealed that rs717620 regulates the expression of ABCC2 in human brain, while drug-gene interaction analysis suggested that ABCC2 interacts with oxcarbazepine and carbamazepine.

Significance

The rs717620 polymorphism influences ASM therapeutic responses by altering brain expression levels of ABCC2.

SUBMITTER: Wang S

PROVIDER: S-EPMC10772244 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

Wang Shitao S Li Zongyou Z Gao Zhibo Z Zhang Mengen M Rao Feng F Lu Jinghong J Xu Hui H Xie Zhenrong Z Ding XiangQian X

Heliyon 20231216 1

<h4>Background</h4>Previous studies have shown that the rs717620 polymorphism in <i>ABCC2</i>, the gene encoding multidrug resistance protein 2, influences the therapeutic response to anti-seizure medications (ASMs). However, this result is not consistent, and the mechanism by which rs717620 influences ASM responses is unclear.<h4>Aims</h4>The present study evaluated the association between rs717620 genotype and ASM efficacy, and examined the potential mechanisms.<h4>Main</h4>methods: We conduct ...[more]

PMID: 38192780

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Project description:BackgroundAnti-seizure medications (ASMs) are the primary therapeutic mode to control seizures in patients with epilepsy. Adherence to the medications is critical to achieving the goals of epilepsy therapy. However, the cost of the medications and the interrupted availability of ASMs contribute to non-adherence to epilepsy treatment. Therefore, this study aimed to assess ASM adherence and its association with self-reported medication availability and affordability.ObjectiveTo assess whether self-reported availability and affordability of Anti-seizure medications affect medication adherence among Epileptic Patients at Eka Kotebe General Hospital, Addis Ababa, Ethiopia, from January 13, 2023 to March 23, 2023.MethodsA hospital-based analytical cross-sectional study was conducted among 357 epileptic patients using the Consecutive sampling method in Eka Kotebe General Hospital, Addis Ababa, Ethiopia. ASM adherence was measured using a self-report 3items questionnaire focusing on medication use patterns of patients from their last visit to the current visit. Statistical packages for Social Sciences 26.0 version statistical software cleaned, coded and analyzed the collected data. Binary logistic regression was fitted, and P-values less than 0.05 were considered to have statistical significance.ResultThe prevalence of ASM adherence was 55.2% with 95% CI (50.1%; 60.2%). About two-thirds (61.3%) of patients in this study had limited access to the ASMs or could not afford the medications. Self-reported availability of ASMs (AOR = 2.01, 95% CI = 1.01, 3.98) was significantly associated with ASM adherence. Self-reported affordability of ASMs was associated with ASM adherence in the Bivariate logistic regression analysis; however, when adjusted for other covariates in the multivariable logistic regression, no significant association was observed (p = 0.674).Conclusion and recommendationOnly about half of the epileptic patients adhered to ASMs at Eka Kotebe General Hospital. Self-reported availability of ASMs was an essential factor. Improving access to ASMs is critical to improving adherence and management of epilepsy.

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Project description:The developmental and epileptic encephalopathies encompass a group of rare syndromes characterised by severe drug-resistant epilepsy with onset in childhood and significant neurodevelopmental comorbidities. The latter include intellectual disability, developmental delay, behavioural problems including attention-deficit hyperactivity disorder and autism spectrum disorder, psychiatric problems including anxiety and depression, speech impairment and sleep problems. Classical examples of developmental and epileptic encephalopathies include Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep. We have performed a targeted literature review of ASMs commonly used in the treatment of developmental and epileptic encephalopathies to discuss the latest evidence on their effects on behaviour, mood, cognition, sedation and sleep. The ASMs include valproate (VPA), clobazam, topiramate (TPM), cannabidiol (CBD), fenfluramine (FFA), levetiracetam (LEV), brivaracetam (BRV), zonisamide (ZNS), perampanel (PER), ethosuximide, stiripentol, lamotrigine (LTG), rufinamide, vigabatrin, lacosamide (LCM) and everolimus. Bromide, felbamate and other sodium channel ASMs are discussed briefly. Overall, the current evidence suggest that LEV, PER and to a lesser extent BRV are associated with psychobehavioural adverse events including aggressiveness and irritability; TPM and to a lesser extent ZNS are associated with language impairment and cognitive dulling/memory problems. Patients with a history of behavioural and psychiatric comorbidities may be more at risk of developing psychobehavioural adverse events. Topiramate and ZNS may be associated with negative effects in some aspects of cognition; CBD, FFA, LEV, BRV and LTG may have some positive effects, while the remaining ASMs do not appear to have a detrimental effect. All the ASMs are associated with sedation to a certain extent, which is pronounced during uptitration. Cannabidiol, PER and pregabalin may be associated with improvements in sleep, LTG is associated with insomnia, while VPA, TPM, LEV, ZNS and LCM do not appear to have detrimental effects. There was variability in the extent of evidence for each ASM: for many first-generation and some second-generation ASMs, there is scant documented evidence; however, their extensive use suggests favourable tolerability and safety (e.g. VPA); second-generation and some third-generation ASMs tend to have the most robust evidence documented over several years of use (TPM, LEV, PER, ZNS, BRV), while evidence is still being generated for newer ASMs such as CBD and FFA. Finally, we discuss how a variety of factors can affect mood, behaviour and cognition, and untangling the associations between the effects of the underlying syndrome and those of the ASMs can be challenging. In particular, there is enormous heterogeneity in cognitive, behavioural and developmental impairments that is complex and can change naturally over time; there is a lack of standardised instruments for evaluating these outcomes in developmental and epileptic encephalopathies, with a reliance on subjective evaluations by proxy (caregivers); and treatment regimes are complex involving multiple ASMs as well as other drugs.

Dataset Information

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

Background

Aims

Main

Key findings

Significance

Publications

Integrative analysis of rs717620 polymorphism in therapeutic response to anti-seizure medications.

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