Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2350-11-162
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dc.titleThe dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project
dc.contributor.authorCombarros, O
dc.contributor.authorWarden, D.R
dc.contributor.authorHammond, N
dc.contributor.authorCortina-Borja, M
dc.contributor.authorBelbin, O
dc.contributor.authorLehmann, M.G
dc.contributor.authorWilcock, G.K
dc.contributor.authorBrown, K
dc.contributor.authorKehoe, P.G
dc.contributor.authorBarber, R
dc.contributor.authorCoto, E
dc.contributor.authorAlvarez, V
dc.contributor.authorDeloukas, P
dc.contributor.authorGwilliam, R
dc.contributor.authorHeun, R
dc.contributor.authorKölsch, H
dc.contributor.authorMateo, I
dc.contributor.authorOulhaj, A
dc.contributor.authorArias-Vásquez, A
dc.contributor.authorSchuur, M
dc.contributor.authorAulchenko, Y.S
dc.contributor.authorIkram, M.A
dc.contributor.authorBreteler, M.M
dc.contributor.authorvan Duijn, C.M
dc.contributor.authorMorgan, K
dc.contributor.authorSmith, A.D
dc.contributor.authorLehmann, D.J
dc.date.accessioned2020-10-27T11:36:06Z
dc.date.available2020-10-27T11:36:06Z
dc.date.issued2010
dc.identifier.citationCombarros, O, Warden, D.R, Hammond, N, Cortina-Borja, M, Belbin, O, Lehmann, M.G, Wilcock, G.K, Brown, K, Kehoe, P.G, Barber, R, Coto, E, Alvarez, V, Deloukas, P, Gwilliam, R, Heun, R, Kölsch, H, Mateo, I, Oulhaj, A, Arias-Vásquez, A, Schuur, M, Aulchenko, Y.S, Ikram, M.A, Breteler, M.M, van Duijn, C.M, Morgan, K, Smith, A.D, Lehmann, D.J (2010). The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project. BMC Medical Genetics 11 (1) : 162. ScholarBank@NUS Repository. https://doi.org/10.1186/1471-2350-11-162
dc.identifier.issn14712350
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/181653
dc.description.abstractBackground: The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine β-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls.Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD.Results: We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain.Conclusions: Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here. © 2010 Combarros et al; licensee BioMed Central Ltd.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectdopamine beta monooxygenase
dc.subjectinterleukin 1alpha
dc.subjectinterleukin 6
dc.subjectnoradrenalin
dc.subjectdopamine beta monooxygenase
dc.subjectIL1A protein, human
dc.subjectinterleukin 1alpha
dc.subjectinterleukin 6
dc.subjectaged
dc.subjectallele
dc.subjectAlzheimer disease
dc.subjectarticle
dc.subjectcontrolled study
dc.subjectfactorial analysis
dc.subjectfemale
dc.subjectgene interaction
dc.subjectgenetic association
dc.subjectgenetic epistasis
dc.subjectgenetic risk
dc.subjectgenotype
dc.subjecthuman
dc.subjectinflammation
dc.subjectlogistic regression analysis
dc.subjectmajor clinical study
dc.subjectmale
dc.subjectregulatory mechanism
dc.subjectsingle nucleotide polymorphism
dc.subjectAlzheimer disease
dc.subjectEurope
dc.subjectgenetics
dc.subjectlocus ceruleus
dc.subjectnerve cell
dc.subjectpathology
dc.subjectrisk
dc.subjectrisk factor
dc.subjectsingle nucleotide polymorphism
dc.subjectSpain
dc.subjectAged
dc.subjectAlzheimer Disease
dc.subjectDopamine beta-Hydroxylase
dc.subjectEpistasis, Genetic
dc.subjectEurope
dc.subjectFemale
dc.subjectGenotype
dc.subjectHumans
dc.subjectInterleukin-1alpha
dc.subjectInterleukin-6
dc.subjectLocus Coeruleus
dc.subjectMale
dc.subjectNeurons
dc.subjectOdds Ratio
dc.subjectPolymorphism, Single Nucleotide
dc.subjectRisk Factors
dc.subjectSpain
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1186/1471-2350-11-162
dc.description.sourcetitleBMC Medical Genetics
dc.description.volume11
dc.description.issue1
dc.description.page162
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