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Article: Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese

TitleGene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese
Authors
KeywordsABCB1
Anti-epileptic drugs
Drug resistance
Epilepsy
P-glycoprotein
Pharmacogenetics
Issue Date2009
PublisherFuture Medicine Ltd. The Journal's web site is located at http://www.futuremedicine.com/loi/pgs
Citation
Pharmacogenomics, 2009, v. 10 n. 5, p. 723-732 How to Cite?
AbstractAims: It remains controversial wether polymorphisms of the multidrug resistance gene ABCB1 are associated with pharmacoresistance in epilepsy. To furtehr study the potential association, we genotyped a broad set of tagging SNPs, and explored whether any associatios were affected by other host factors. We correlated any association with cerebral mRNA expression of ABCB1. Materials & methods: A total of 12 tagging and candidate SNPs of ABCB1 were genotyped in 464 Chinese epilepsy patients (270 drug responsive, 194 drug resistant). Genotype and allele distributions in drug-response and drug-resistant patients were compared. ABCB1 mRNA was quantified by real-time PCR in brain samples resected from 20 patients with drug-resistant epilepsy. Its level was compared between patients with different genotypes of ABCB1S SNPs found to be associated with drug resistance. Results: The intronic polymorphism rs3789243 (p = 0.009 for allele analysis) and the coding polymorphism 2677G/T/A (p = 0.02), and haplotypes containing them, were associated with drug resistance. The 2677G/T/A genotypes remained significantly associated with drug resistance after multiple logistic regression and correction for multiple comparisons. The associations with drug resistance were found in males (p = 0.004 for rs3789243 and p = 0.0007 for for 2677T/A>G) but not females, and in patients with localization-related (p = 0.006 for rs3789243 and p = 0.01 for 2677T/A>G) but not idiopathic-generalized epilepsy. ABCB1 mRNA levels did not correlate with genotypes. Conclusion: In Chinese epilepsy patients, the ABCB1 intronic polymorphism rs3789243 and the coding polymorphism 2677, and haplotypes containing them, may be associated with drug resistance, without an effect on mRNA expression. There was preliminary evidence of interactions between these polymorphisms and gender and epilepsy syndrome. © 2009 Future Medicine Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/59502
ISSN
2015 Impact Factor: 2.71
2015 SCImago Journal Rankings: 0.932
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of the Hong Kong Special Administrative Region, ChinaCUHK4466/06M
Funding Information:

The work described in the paper was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. CUHK4466/06M). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

References

 

DC FieldValueLanguage
dc.contributor.authorKwan, Pen_HK
dc.contributor.authorWong, Ven_HK
dc.contributor.authorNg, PWen_HK
dc.contributor.authorLui, CHTen_HK
dc.contributor.authorSin, NCen_HK
dc.contributor.authorPoon, WSen_HK
dc.contributor.authorNg, HKen_HK
dc.contributor.authorWong, KSen_HK
dc.contributor.authorBaum, Len_HK
dc.date.accessioned2010-05-31T03:51:34Z-
dc.date.available2010-05-31T03:51:34Z-
dc.date.issued2009en_HK
dc.identifier.citationPharmacogenomics, 2009, v. 10 n. 5, p. 723-732en_HK
dc.identifier.issn1462-2416en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59502-
dc.description.abstractAims: It remains controversial wether polymorphisms of the multidrug resistance gene ABCB1 are associated with pharmacoresistance in epilepsy. To furtehr study the potential association, we genotyped a broad set of tagging SNPs, and explored whether any associatios were affected by other host factors. We correlated any association with cerebral mRNA expression of ABCB1. Materials & methods: A total of 12 tagging and candidate SNPs of ABCB1 were genotyped in 464 Chinese epilepsy patients (270 drug responsive, 194 drug resistant). Genotype and allele distributions in drug-response and drug-resistant patients were compared. ABCB1 mRNA was quantified by real-time PCR in brain samples resected from 20 patients with drug-resistant epilepsy. Its level was compared between patients with different genotypes of ABCB1S SNPs found to be associated with drug resistance. Results: The intronic polymorphism rs3789243 (p = 0.009 for allele analysis) and the coding polymorphism 2677G/T/A (p = 0.02), and haplotypes containing them, were associated with drug resistance. The 2677G/T/A genotypes remained significantly associated with drug resistance after multiple logistic regression and correction for multiple comparisons. The associations with drug resistance were found in males (p = 0.004 for rs3789243 and p = 0.0007 for for 2677T/A>G) but not females, and in patients with localization-related (p = 0.006 for rs3789243 and p = 0.01 for 2677T/A>G) but not idiopathic-generalized epilepsy. ABCB1 mRNA levels did not correlate with genotypes. Conclusion: In Chinese epilepsy patients, the ABCB1 intronic polymorphism rs3789243 and the coding polymorphism 2677, and haplotypes containing them, may be associated with drug resistance, without an effect on mRNA expression. There was preliminary evidence of interactions between these polymorphisms and gender and epilepsy syndrome. © 2009 Future Medicine Ltd.en_HK
dc.languageengen_HK
dc.publisherFuture Medicine Ltd. The Journal's web site is located at http://www.futuremedicine.com/loi/pgsen_HK
dc.relation.ispartofPharmacogenomicsen_HK
dc.subjectABCB1en_HK
dc.subjectAnti-epileptic drugsen_HK
dc.subjectDrug resistanceen_HK
dc.subjectEpilepsyen_HK
dc.subjectP-glycoproteinen_HK
dc.subjectPharmacogeneticsen_HK
dc.titleGene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chineseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1462-2416&volume=10&issue=5&spage=723&epage=732&date=2009&atitle=Gene-wide+tagging+study+of+association+between+ABCB1+polymorphisms+and+multidrug+resistance+in+epilepsy+in+Han+Chineseen_HK
dc.identifier.emailWong, V:vcnwong@hku.hken_HK
dc.identifier.authorityWong, V=rp00334en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.2217/pgs.09.32en_HK
dc.identifier.pmid19450124-
dc.identifier.scopuseid_2-s2.0-66849129225en_HK
dc.identifier.hkuros162272en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-66849129225&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue5en_HK
dc.identifier.spage723en_HK
dc.identifier.epage732en_HK
dc.identifier.isiWOS:000267091700006-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridKwan, P=7004369601en_HK
dc.identifier.scopusauthoridWong, V=7202525632en_HK
dc.identifier.scopusauthoridNg, PW=7201376949en_HK
dc.identifier.scopusauthoridLui, CHT=36943011700en_HK
dc.identifier.scopusauthoridSin, NC=6602256513en_HK
dc.identifier.scopusauthoridPoon, WS=7103025507en_HK
dc.identifier.scopusauthoridNg, HK=7401619354en_HK
dc.identifier.scopusauthoridWong, KS=7404759405en_HK
dc.identifier.scopusauthoridBaum, L=7103310839en_HK
dc.identifier.citeulike4623892-

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