Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression

Kwan, Patrick; Poon, Wai Sang; Ng, Ho Keung; Kang, David E.; Wong, Virginia; Ng, Ping Wing; Lui, Colin H.T.; Sin, Ngai Chuen; Wong, Ka Sing; Baum, Larry

doi:10.1097/fpc.0b013e3283117d67

Cited by 113 publications

(64 citation statements)

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“…[11][12][13] Studies examining SCN1A genotype and clinical response have likewise focused primarily on the rs3812718 polymorphism with some examining the non-synonymous single-nucleotide polymorphism (SNP), rs2298771 (3199A4G), and have failed to demonstrate any associations. 11,[14][15][16][17][18][19][20] To date, only Kwan and colleagues 20 have used a haplotype tagging methodology to fully examine SCN1A variations and clinical response to sodium channel blocking drugs. They found no SCN1A associations in their group of Chinese epilepsy patients.…”

Section: Introductionmentioning

confidence: 99%

SCN1A variations and response to multiple antiepileptic drugs

et al. 2013

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In the current study, we have used the haplotype-tagging single-nucleotide polymorphisms (SNPs) to determine associations between genetic variants in SCN1A and treatment response in 519 Caucasian patients with known response status for epilepsy treated with antiepileptic drugs (AEDs) with sodium channel blocking effects. Nine SNPs within SCN1A were genotyped in this cohort. The only association observed was for rs10188577. A greater proportion of drug-resistant patients were heterozygous compared with drug responsive patients (48.3% vs 35.4%, P=0.014). After correction for potential confounding factors, the association for rs10188577 was only marginally significant (P=0.049). In light of our findings, it seems unlikely that rs10188577 could be a major determinant of response to AEDs. However, looking at the influence of rs10188577 on the expressed quantitative trait association patterns within the immediate vicinity of SCN1A, we found significant associations with neighbouring sodium channel genes, SCN7A and SCN9A (P<0.025), which warrants further studies.

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Section: Introductionmentioning

confidence: 99%

SCN1A variations and response to multiple antiepileptic drugs

et al. 2013

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“…Use-dependent blockade of the fast Na current in dentate granule cells by carbamazepine is lost in hippocampi resected from patients with carbamazepine-resistant temporal-lobe epilepsy, although this fi nding does not extend to lamotrigine, which has a pharmacologic action similar to that of carbamazepine. Polymorphisms of the SCN2A gene, which encodes the α2 subunit of the neuronal Na channels, were found to be associated with resistance to AEDs in general as well as to those that act on the sodium channels (Kwan et al 2008 ). Whether these changes result in reduced sensitivity to antiepileptic drugs that act on the receptor is unknown.…”

Section: Drug Resistance In Epilepsymentioning

confidence: 98%

Textbook of Personalized Medicine

Jain¹

2015

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“…However, another study conducted in Japanese revealed a positive association between the genetic variation of IVS5-19 G>A and CBZ resistance [13]. In addition, a study has reported a positive association between SNP of SCN2A IVS7-32 G>A and AED resistance in Hong Kong Chinese [14]. Nevertheless, there is as yet no definite evidence suggesting the association between the genetic variation of SCN1A and the different responses to AED Other AED targets, where functional polymorphisms could possibly influence the clinical treatment response, are GABA A receptors.…”

Section: Genetic Variations In Individuals That May Affect Pharmacodymentioning

confidence: 99%

Genetic variations and response to antiepileptic drug

Kim

2010

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Despite the state-of-the-art medical treatment with antiepileptic drugs (AED), at least one-third of newly diagnosed epilepsy patients may show poor response to AED. Although the biological mechanism of diverse responses to AED is poorly understood, it is likely that multifactorial factors could be responsible for the different responses. Clinical factors such as etiology of epilepsy and pre-treatment seizure frequency can predict the different responses to AED, whereas the role of genetic variations in individuals contributing to variation in response to AED is still conflicting. The inconsistency in proving the genetic roles in different responses to AED may be partly explained by (1) diversity of the definition of response to AED, (2) heterogeneity of the subjects, and (3) lack of multigenetic approach. While we hypothesize that the genetic variations in individuals may independently contribute to different responses to AED, multigenetic interactions including both the genetic variations of pharmacokinetics and pharmacodynamics may take place.

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Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression

Abstract: Results of this study suggest an association between SCN2A IVS7-32A>G and AED responsiveness, without evidence of an effect on splicing or mRNA expression.

Cited by 113 publications

References 24 publications

SCN1A variations and response to multiple antiepileptic drugs

SCN1A variations and response to multiple antiepileptic drugs

Textbook of Personalized Medicine

Genetic variations and response to antiepileptic drug

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