File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Evidence for association between polymorphisms in the promoter and coding regions of the 5-HT(2A) receptor gene and response to clozapine

TitleEvidence for association between polymorphisms in the promoter and coding regions of the 5-HT(2A) receptor gene and response to clozapine
Authors
Issue Date1998
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 1998, v. 3 n. 1, p. 61-66 How to Cite?
AbstractClozapine is a potent atypical antipsychotic which binds to a variety of neurotransmitter receptors including serotonin (5-HT) receptors. However, the precise neurochemical site of clozapine's therapeutic action is unknown. We hypothesize that genetic variation in the neurotransmitter receptors to which the drug binds may influence clozapine response. To test this hypothesis we genotyped a novel -1438-G/A polymorphism detected in the promoter region, and a His452Tyr polymorphism described in the coding region of the 5-HT(2A) receptor gene in two independent samples of clozapine-treated patients including responders and non-responders. Although the strong association between these polymorphisms and clozapine response observed in the first sample (sample I) was not statistically significant in the second sample (sample II), the results in both samples were in the same direction. Homozygosity for the allele G-1438 was higher among non-responders (56% in sample I, 43% in sample II) than in responders (28% in sample I and 32% in sample II) in both samples. Similarly, the frequency of allele Tyr452 was higher in non-responders (11% in sample I, 16% in sample II) than in responders (6% in sample I and 10% in sample II). A combined analysis of both samples showed association between both polymorphisms and clozapine response. These results provide further evidence suggesting that genetic variation at 5-HT(2A) receptors may influence clozapine response and strengthen the candidacy of these receptors as important therapeutic targets.
Persistent Identifierhttp://hdl.handle.net/10722/175785
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorArranz, MJen_US
dc.contributor.authorMunro, Jen_US
dc.contributor.authorOwen, MJen_US
dc.contributor.authorSpurlock, Gen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorZhao, Jen_US
dc.contributor.authorKirov, Gen_US
dc.contributor.authorCollier, DAen_US
dc.contributor.authorKerwin, RWen_US
dc.date.accessioned2012-11-26T09:01:16Z-
dc.date.available2012-11-26T09:01:16Z-
dc.date.issued1998en_US
dc.identifier.citationMolecular Psychiatry, 1998, v. 3 n. 1, p. 61-66en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175785-
dc.description.abstractClozapine is a potent atypical antipsychotic which binds to a variety of neurotransmitter receptors including serotonin (5-HT) receptors. However, the precise neurochemical site of clozapine's therapeutic action is unknown. We hypothesize that genetic variation in the neurotransmitter receptors to which the drug binds may influence clozapine response. To test this hypothesis we genotyped a novel -1438-G/A polymorphism detected in the promoter region, and a His452Tyr polymorphism described in the coding region of the 5-HT(2A) receptor gene in two independent samples of clozapine-treated patients including responders and non-responders. Although the strong association between these polymorphisms and clozapine response observed in the first sample (sample I) was not statistically significant in the second sample (sample II), the results in both samples were in the same direction. Homozygosity for the allele G-1438 was higher among non-responders (56% in sample I, 43% in sample II) than in responders (28% in sample I and 32% in sample II) in both samples. Similarly, the frequency of allele Tyr452 was higher in non-responders (11% in sample I, 16% in sample II) than in responders (6% in sample I and 10% in sample II). A combined analysis of both samples showed association between both polymorphisms and clozapine response. These results provide further evidence suggesting that genetic variation at 5-HT(2A) receptors may influence clozapine response and strengthen the candidacy of these receptors as important therapeutic targets.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mpen_US
dc.relation.ispartofMolecular Psychiatryen_US
dc.subject.meshAllelesen_US
dc.subject.meshAntipsychotic Agents - Therapeutic Useen_US
dc.subject.meshClozapine - Therapeutic Useen_US
dc.subject.meshDrug Resistance - Geneticsen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHumansen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPolymorphism, Geneticen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshReceptor, Serotonin, 5-Ht2aen_US
dc.subject.meshReceptors, Serotonin - Geneticsen_US
dc.subject.meshReference Valuesen_US
dc.subject.meshSchizophrenia - Drug Therapy - Geneticsen_US
dc.titleEvidence for association between polymorphisms in the promoter and coding regions of the 5-HT(2A) receptor gene and response to clozapineen_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.mp.4000348-
dc.identifier.pmid9491814-
dc.identifier.scopuseid_2-s2.0-0031963472en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031963472&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume3en_US
dc.identifier.issue1en_US
dc.identifier.spage61en_US
dc.identifier.epage66en_US
dc.identifier.isiWOS:000073470400014-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridArranz, MJ=7006010757en_US
dc.identifier.scopusauthoridMunro, J=7102726057en_US
dc.identifier.scopusauthoridOwen, MJ=36044041500en_US
dc.identifier.scopusauthoridSpurlock, G=7003802827en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridZhao, J=7410311266en_US
dc.identifier.scopusauthoridKirov, G=26643478800en_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US
dc.identifier.scopusauthoridKerwin, RW=7102904567en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats