File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

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

TitleMultidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: Correlation among phenotype, genotype, and mRNA expression
Authors
KeywordsAntiepileptic drug
Drug resistance
Epilepsy
Pharmacogenetic
Sodium channel
Issue Date2008
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jpharmacogenetics.com
Citation
Pharmacogenetics And Genomics, 2008, v. 18 n. 11, p. 989-998 How to Cite?
AbstractObjectives Many antiepileptic drugs (AEDs) prevent seizures by blocking voltage-gated brain sodium channels. However, treatment is ineffective in 30% of epilepsy patients, which might, at least in part, result from polymorphisms of the sodium channel genes. We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels. Methods We performed genotyping of tagging and candidate single nucleotide polymorphisms (SNPs) of SCN1A, 2A, and 3A in 471 Chinese epilepsy patients (272 drug responsive and 199 drug resistant). A total of 27 SNPs were selected based on the HapMap database. Genotype distributions in drug-responsive and drug-resistant patients were compared. SCN2A mRNA was quantified by real-time PCR in 24 brain and 57 blood samples. Its level was compared between patients with different genotypes of an SCN2A SNP found to be associated with drug responsiveness. Results SCN2A IVS7-32A>G (rs2304016) A alleles were associated with drug resistance (odds ratio = 2.1, 95% confidence interval: 1.2-3.7, P=0.007). Haplotypes containing the IVS7-32A>G allele A were also associated with drug resistance. IVS7-32A>G is located within the putative splicing branch site for splicing exons 7 and 9. PCR of reverse-transcribed RNA from blood or brain of patients with different IVS7-32A>G genotypes using primers in exons 7 and 9 showed no skipping of exon 8, and real-time PCR showed no difference in SCN2A mRNA levels among genotypes. Conclusion 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. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins.
Persistent Identifierhttp://hdl.handle.net/10722/59516
ISSN
2015 Impact Factor: 2.857
2015 SCImago Journal Rankings: 1.194
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilCUHK4466/06M
Funding Information:

PK. is supported by the Hong Kong Research Grants Council Clinical Research Fellowship Grant (CERG Project CUHK4466/06M).

References

 

DC FieldValueLanguage
dc.contributor.authorKwan, Pen_HK
dc.contributor.authorPoon, WSen_HK
dc.contributor.authorNg, HKen_HK
dc.contributor.authorKang, DEen_HK
dc.contributor.authorWong, Ven_HK
dc.contributor.authorNg, PWen_HK
dc.contributor.authorLui, CHTen_HK
dc.contributor.authorSin, NCen_HK
dc.contributor.authorWong, KSen_HK
dc.contributor.authorBaum, Len_HK
dc.date.accessioned2010-05-31T03:51:49Z-
dc.date.available2010-05-31T03:51:49Z-
dc.date.issued2008en_HK
dc.identifier.citationPharmacogenetics And Genomics, 2008, v. 18 n. 11, p. 989-998en_HK
dc.identifier.issn1744-6872en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59516-
dc.description.abstractObjectives Many antiepileptic drugs (AEDs) prevent seizures by blocking voltage-gated brain sodium channels. However, treatment is ineffective in 30% of epilepsy patients, which might, at least in part, result from polymorphisms of the sodium channel genes. We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels. Methods We performed genotyping of tagging and candidate single nucleotide polymorphisms (SNPs) of SCN1A, 2A, and 3A in 471 Chinese epilepsy patients (272 drug responsive and 199 drug resistant). A total of 27 SNPs were selected based on the HapMap database. Genotype distributions in drug-responsive and drug-resistant patients were compared. SCN2A mRNA was quantified by real-time PCR in 24 brain and 57 blood samples. Its level was compared between patients with different genotypes of an SCN2A SNP found to be associated with drug responsiveness. Results SCN2A IVS7-32A>G (rs2304016) A alleles were associated with drug resistance (odds ratio = 2.1, 95% confidence interval: 1.2-3.7, P=0.007). Haplotypes containing the IVS7-32A>G allele A were also associated with drug resistance. IVS7-32A>G is located within the putative splicing branch site for splicing exons 7 and 9. PCR of reverse-transcribed RNA from blood or brain of patients with different IVS7-32A>G genotypes using primers in exons 7 and 9 showed no skipping of exon 8, and real-time PCR showed no difference in SCN2A mRNA levels among genotypes. Conclusion 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. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins.en_HK
dc.languageengen_HK
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.jpharmacogenetics.comen_HK
dc.relation.ispartofPharmacogenetics and Genomicsen_HK
dc.rightsPharmacogenetics and Genomics. Copyright © Lippincott Williams & Wilkins.en_HK
dc.subjectAntiepileptic drugen_HK
dc.subjectDrug resistanceen_HK
dc.subjectEpilepsyen_HK
dc.subjectPharmacogeneticen_HK
dc.subjectSodium channelen_HK
dc.titleMultidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: Correlation among phenotype, genotype, and mRNA expressionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1744-6872&volume=18&spage=989&epage=998&date=2008&atitle=Multidrug+resistance+in+epilepsy+and+polymorphisms+in+the+voltage-gated+sodium+channel+genes+SCN1A,+SCN2A,+and+SCN3A:+correlation+among+phenotype,+genotype,+and+mRNA+expressionen_HK
dc.identifier.emailWong, V:vcnwong@hku.hken_HK
dc.identifier.authorityWong, V=rp00334en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1097/FPC.0b013e3283117d67en_HK
dc.identifier.pmid18784617-
dc.identifier.scopuseid_2-s2.0-56149108008en_HK
dc.identifier.hkuros155736en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-56149108008&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue11en_HK
dc.identifier.spage989en_HK
dc.identifier.epage998en_HK
dc.identifier.isiWOS:000260553500007-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridKwan, P=7004369601en_HK
dc.identifier.scopusauthoridPoon, WS=7103025507en_HK
dc.identifier.scopusauthoridNg, HK=7401619354en_HK
dc.identifier.scopusauthoridKang, DE=7402889417en_HK
dc.identifier.scopusauthoridWong, V=7202525632en_HK
dc.identifier.scopusauthoridNg, PW=7201376949en_HK
dc.identifier.scopusauthoridLui, CHT=7006065991en_HK
dc.identifier.scopusauthoridSin, NC=6602256513en_HK
dc.identifier.scopusauthoridWong, KS=7404759405en_HK
dc.identifier.scopusauthoridBaum, L=7103310839en_HK
dc.identifier.citeulike5190113-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats