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Article: A novel functional polymorphism within the promoter of the serotonin transporter gene: Possible role in susceptibility to affective disorders

TitleA novel functional polymorphism within the promoter of the serotonin transporter gene: Possible role in susceptibility to affective disorders
Authors
Issue Date1996
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 1996, v. 1 n. 6, p. 453-460 How to Cite?
AbstractThe serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessivity of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
Persistent Identifierhttp://hdl.handle.net/10722/175764
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCollier, DAen_US
dc.contributor.authorStöber, Gen_US
dc.contributor.authorLi, Ten_US
dc.contributor.authorHeils, Aen_US
dc.contributor.authorCatalano, Men_US
dc.contributor.authorDi Bella, Den_US
dc.contributor.authorArranz, MJen_US
dc.contributor.authorMurray, RMen_US
dc.contributor.authorVallada, HPen_US
dc.contributor.authorBengel, Den_US
dc.contributor.authorMüller, CRen_US
dc.contributor.authorRoberts, GWen_US
dc.contributor.authorSmeraldi, Een_US
dc.contributor.authorKirov, Gen_US
dc.contributor.authorSham, Pen_US
dc.contributor.authorLesch, KPen_US
dc.date.accessioned2012-11-26T09:01:07Z-
dc.date.available2012-11-26T09:01:07Z-
dc.date.issued1996en_US
dc.identifier.citationMolecular Psychiatry, 1996, v. 1 n. 6, p. 453-460en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175764-
dc.description.abstractThe serotonin transporter (5-HTT) is a candidate locus for aetiological involvement in affective disorders. Biochemical studies in suicides and depressed patients suggest that 5-HT uptake function is frequently reduced in affective illness. Furthermore, 5-HTT is targeted by widely used antidepressant drugs such as fluoxetine. We have performed an association study of a short variant of the 5-HTT-linked polymorphic region (5-HTTLPR), which restricts transcriptional activity of the 5-HTT promoter leading to low functional expression of the 5-HTT, in 454 patients with bipolar or unipolar affective disorder and 570 controls, derived from three European Centres (London, Milan and Würzburg). In all three centres, the frequency of the low activity allele was higher in patients than in controls (50% vs 45% in London, 45% vs 43% in Milan, 47% vs 40% in Würzburg). Although these differences were not individually significant, a stratified analysis of all three samples gave a significant overall odds ratio of 1.23 (95% confidence interval 1.02-1.49, P = 0.03). The excess of the homozygous low-activity genotype among the patients was even greater (odds ratio 1.53, 95% confidence interval 1.04-2.23, P = 0.02), suggesting partial recessivity of the low-activity allele. Given the functional role of 5-HTT, our findings suggest that 5-HTTLPR-dependent variation in functional 5-HTT expression is a potential genetic susceptibility factor for affective disorders. If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.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.meshBipolar Disorder - Genetics - Metabolismen_US
dc.subject.meshCarrier Proteins - Geneticsen_US
dc.subject.meshCase-Control Studiesen_US
dc.subject.meshDepression - Genetics - Metabolismen_US
dc.subject.meshEuropeen_US
dc.subject.meshGene Frequencyen_US
dc.subject.meshGenetic Linkageen_US
dc.subject.meshGenotypeen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHumansen_US
dc.subject.meshMembrane Glycoproteins - Geneticsen_US
dc.subject.meshMembrane Transport Proteinsen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNerve Tissue Proteins - Genetics - Metabolismen_US
dc.subject.meshPhenotypeen_US
dc.subject.meshPolymorphism, Genetic - Geneticsen_US
dc.subject.meshPromoter Regions, Genetic - Physiologyen_US
dc.subject.meshSerotonin - Genetics - Metabolismen_US
dc.subject.meshSerotonin Plasma Membrane Transport Proteinsen_US
dc.subject.meshTranscriptional Activation - Geneticsen_US
dc.titleA novel functional polymorphism within the promoter of the serotonin transporter gene: Possible role in susceptibility to affective disordersen_US
dc.typeArticleen_US
dc.identifier.emailSham, P: pcsham@hku.hken_US
dc.identifier.authoritySham, P=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid9154246-
dc.identifier.scopuseid_2-s2.0-0030320649en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030320649&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume1en_US
dc.identifier.issue6en_US
dc.identifier.spage453en_US
dc.identifier.epage460en_US
dc.identifier.isiWOS:A1996VZ75700010-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US
dc.identifier.scopusauthoridStöber, G=7006436754en_US
dc.identifier.scopusauthoridLi, T=36072008200en_US
dc.identifier.scopusauthoridHeils, A=7003263405en_US
dc.identifier.scopusauthoridCatalano, M=7102930027en_US
dc.identifier.scopusauthoridDi Bella, D=7003903937en_US
dc.identifier.scopusauthoridArranz, MJ=7006010757en_US
dc.identifier.scopusauthoridMurray, RM=35406239400en_US
dc.identifier.scopusauthoridVallada, HP=7003742958en_US
dc.identifier.scopusauthoridBengel, D=6701760591en_US
dc.identifier.scopusauthoridMüller, CR=7404110456en_US
dc.identifier.scopusauthoridRoberts, GW=7403400681en_US
dc.identifier.scopusauthoridSmeraldi, E=7101814406en_US
dc.identifier.scopusauthoridKirov, G=26643478800en_US
dc.identifier.scopusauthoridSham, P=34573429300en_US
dc.identifier.scopusauthoridLesch, KP=19735689200en_US

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