Please use this identifier to cite or link to this item: https://doi.org/10.1186/1471-2350-11-162
Title: The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project
Authors: Combarros, 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
Keywords: dopamine beta monooxygenase
interleukin 1alpha
interleukin 6
noradrenalin
dopamine beta monooxygenase
IL1A protein, human
interleukin 1alpha
interleukin 6
aged
allele
Alzheimer disease
article
controlled study
factorial analysis
female
gene interaction
genetic association
genetic epistasis
genetic risk
genotype
human
inflammation
logistic regression analysis
major clinical study
male
regulatory mechanism
single nucleotide polymorphism
Alzheimer disease
Europe
genetics
locus ceruleus
nerve cell
pathology
risk
risk factor
single nucleotide polymorphism
Spain
Aged
Alzheimer Disease
Dopamine beta-Hydroxylase
Epistasis, Genetic
Europe
Female
Genotype
Humans
Interleukin-1alpha
Interleukin-6
Locus Coeruleus
Male
Neurons
Odds Ratio
Polymorphism, Single Nucleotide
Risk Factors
Spain
Issue Date: 2010
Citation: Combarros, 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
Rights: Attribution 4.0 International
Abstract: Background: 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.
Source Title: BMC Medical Genetics
URI: https://scholarbank.nus.edu.sg/handle/10635/181653
ISSN: 14712350
DOI: 10.1186/1471-2350-11-162
Rights: Attribution 4.0 International
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