期刊
EUROPEAN JOURNAL OF HUMAN GENETICS
卷 22, 期 2, 页码 216-220出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ejhg.2013.116
关键词
healthy cell bias; C18; dementia; neurodegeneration
资金
- Moulton Charitable Foundation
- NIHR Biomedical Research Centre Oxford
- Medical Research Council
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for Scientific Research (NWO)
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Netherlands Genomics Initiative
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission
- Municipality of Rotterdam
- Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Alzheimers Research UK [ARUK-PG2014-2, ARUK-TRFUS2012-1, ART-BIG2009-1, ARUK-NCG2014A-1, ART-SB2010A-1] Funding Source: researchfish
- Medical Research Council [MR/L022656/1] Funding Source: researchfish
- MRC [MR/L022656/1] Funding Source: UKRI
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据