The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project

Autor: Patrick G. Kehoe, M. Arfan Ikram, Mario Cortina-Borja, Naomi Hammond, A. David Smith, Reinhard Heun, Panos Deloukas, Rachel Barber, Yurii S. Aulchenko, Monique M.B. Breteler, Maaike Schuur, Eliecer Coto, Kristelle Brown, Cornelia M. van Duijn, Olivia Belbin, D J Lehmann, Heike Kölsch, Michael G Lehmann, Alejandro Arias-Vásquez, Gordon K. Wilcock, Donald Warden, Abderrahim Oulhaj, Ignacio Mateo, Rhian Gwilliam, Onofre Combarros, Victoria Alvarez, Kevin Morgan
Přispěvatelé: Neurology, Epidemiology, Universidad de Cantabria
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: BMC Medical Genetics, 11, pp. 162-162
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, vol. 11, no. 1, 162 . https://doi.org/10.1186/1471-2350-11-162
BMC Medical Genetics, 11, 162-162
BMC Medical Genetics, Vol 11, Iss 1, p 162 (2010)
BMC Medical Genetics, 11. BioMed Central Ltd.
BMC Medical Genetics. 2010 Nov 11;11:162
UCrea Repositorio Abierto de la Universidad de Cantabria
Universidad de Cantabria (UC)
BMC Medical Genetics, 11(1):162. BioMed Central
BMC Medical Genetics
ISSN: 1471-2350
Popis: 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.
Databáze: OpenAIRE
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