ArticleBMC medical genetics2010
The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project.
Article in BMC medical genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.Neuromolecular medicine · 2025Pooled it
- The catecholamine biosynthetic enzyme dopamine β-hydroxylase (DBH): first genome-wide search positions trait-determining variants acting additively in the proximal promoter.Human molecular genetics · 2014Pooled it
- Associations Between Dopamine Beta-Hydroxylase Gene Polymorphisms and Restless Legs Syndrome: A Case-Control Study.Medical science monitor : international medical journal of experimental and clinical research · 2025Article
- Neuromodulation of Dopamine D2 Receptors Alters Orbitofrontal Neuronal Activity and Reduces Risk-Prone Behavior in Male Rats with Inflammatory Pain.Molecular neurobiology · 2025Article
- A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation.Antioxidants (Basel, Switzerland) · 2025Review
- Multifactor Dimensionality Reduction Analysis to Evaluate the Association of Dopamine Beta-Hydroxylase (DΒH) Polymorphisms with Susceptibility to Dementia (SADEM Study).Molecular neurobiology · 2023Article
- Candidate gene association study suggests potential role of dopamine beta-hydroxylase in pain heterogeneity in sickle cell disease.Frontiers in genetics · 2023Article
- Comprehensive analysis of immune-related biomarkers and pathways in intracerebral hemorrhage using weighted gene co-expression network analysis and competing endogenous ribonucleic acid.Frontiers in molecular neuroscience · 2022Article
- Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- The mechanistic link between selective vulnerability of the locus coeruleus and neurodegeneration in Alzheimer's disease.Acta neuropathologica · 2021Review
- Relationships of Cerebrospinal Fluid Alzheimer's Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms.Journal of Alzheimer's disease : JAD · 2020Article
- The Presynaptic Regulation of Dopamine and Norepinephrine Synthesis Has Dissociable Effects on Different Kinds of Cognitive Conflicts.Molecular neurobiology · 2019Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Evolutionary footprint of epistasis.PLoS computational biology · 2018Article
- Stress induced neural reorganization: A conceptual framework linking depression and Alzheimer's disease.Progress in neuro-psychopharmacology & biological psychiatry · 2018Review
- Acupuncture Rescues Cognitive Impairment and Upregulates Dopamine-BioMed research international · 2018Article
- Genetic polymorphisms of interleukin genes and the risk of Alzheimer's disease: An update meta-analysis.Meta gene · 2016Article
- Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium.Neurobiology of aging · 2016Article
- Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases.Frontiers in neuroscience · 2016Review
- MOXD2, a Gene Possibly Associated with Olfaction, Is Frequently Inactivated in Birds.PloS one · 2016Article
Corrections and comments
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Authors and funding
27 authors at 13 institutions in 4 countries.
Funding
Abstract
backgroundThe 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.
methodsWe 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.
resultsWe 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.
conclusionsExtensive, 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.