ArticleEuropean journal of human genetics : EJHG2014
The sex-specific associations of the aromatase gene with Alzheimer's disease and its interaction with IL10 in the Epistasis Project.
Article in European journal of human genetics : EJHG, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Association between rs10046, rs1143704, rs767199, rs727479, rs1065778, rs1062033, rs1008805, and rs700519 polymorphisms in aromatase (CYP19A1) gene and Alzheimer's disease risk: a systematic review and meta-analysis involving 11,051 subjects.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Pooled it
- Sex-specific associations between astrocytic reactivity and cognitive decline in unimpaired elderly.bioRxiv : the preprint server for biology · 2026Article
- CSF estrogens' relationships to neuroinflammatory markers and brain networks in middle-aged and older black and white women.Journal of neuroinflammation · 2025Article
- Sexual and Metabolic Differences in Hippocampal Evolution: Alzheimer's Disease Implications.Life (Basel, Switzerland) · 2024Review
- Ovarian steroid hormones: A long overlooked but critical contributor to brain aging and Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- PET imaging of brain aromatase in humans and rhesus monkeys byScientific reports · 2021Article
- Aromatase in the Human Brain.Androgens: clinical research and therapeutics · 2021Review
- Sex-dependent effect ofDisease models & mechanisms · 2020Review
- Steroids and Alzheimer's Disease: Changes Associated with Pathology and Therapeutic Potential.International journal of molecular sciences · 2020Review
- Genome-wide prediction and prioritization of human aging genes by data fusion: a machine learning approach.BMC genomics · 2019Article
- Interactions of Aromatase and Seladin-1: A Neurosteroidogenic and Gender Perspective.Translational neuroscience · 2019Article
- Ovarian Hormone-Dependent Effects of Dietary Lipids on APP/PS1 Mouse Brain.Frontiers in aging neuroscience · 2019Article
- Male-specific epistasis between WWC1 and TLN2 genes is associated with Alzheimer's disease.Neurobiology of aging · 2018Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study.Movement disorders : official journal of the Movement Disorder Society · 2018Article
- Cognitive Effects of Aromatase and Possible Role in Memory Disorders.Frontiers in endocrinology · 2018Review
- Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses.Frontiers in molecular neuroscience · 2018Review
- Epidemiology of estrogen and dementia in women with Down syndrome.Free radical biology & medicine · 2018Review
- Interactions between inflammation, sex steroids, and Alzheimer's disease risk factors.Frontiers in neuroendocrinology · 2016Review
- Inflammatory Cytokines and Alzheimer's Disease: A Review from the Perspective of Genetic Polymorphisms.Neuroscience bulletin · 2016Review
Corrections and comments
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Authors and funding
27 authors at 12 institutions in 4 countries.
Funding
Abstract
Epistasis between interleukin-10 (IL10) and aromatase gene polymorphisms has previously been reported to modify the risk of Alzheimer's disease (AD). However, although the main effects of aromatase variants suggest a sex-specific effect in AD, there has been insufficient power to detect sex-specific epistasis between these genes to date. Here we used the cohort of 1757 AD patients and 6294 controls in the Epistasis Project. We replicated the previously reported main effects of aromatase polymorphisms in AD risk in women, for example, adjusted odds ratio of disease for rs1065778 GG=1.22 (95% confidence interval: 1.01-1.48, P=0.03). We also confirmed a reported epistatic interaction between IL10 rs1800896 and aromatase (CYP19A1) rs1062033, again only in women: adjusted synergy factor=1.94 (1.16-3.25, 0.01). Aromatase, a rate-limiting enzyme in the synthesis of estrogens, is expressed in AD-relevant brain regions ,and is downregulated during the disease. IL-10 is an anti-inflammatory cytokine. Given that estrogens have neuroprotective and anti-inflammatory activities and regulate microglial cytokine production, epistasis is biologically plausible. Diminishing serum estrogen in postmenopausal women, coupled with suboptimal brain estrogen synthesis, may contribute to the inflammatory state, that is a pathological hallmark of AD.
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