Estrogen receptor α gene polymorphisms and risk of Alzheimer’s disease: evidence from a meta-analysis

Abstract

ObjectiveHuman estrogen receptor α (ESR1), a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) – are possibly associated with Alzheimer’s disease (AD). However, individual study results are still controversial.Materials and methodsWe searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD.ResultsThe results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P=0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05).ConclusionBased on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger studies.

Genetic Polymorphisms in Estrogen Metabolic Pathway Associated with Risks of Alzheimer's Disease: Evidence from a Southern Chinese Population

“…Similar to previous findings, no association was found between AD and rs2234693 in this Chinese population. This finding is also consistent with a recent meta‐analysis that found the rs2234693 was associated with risk of AD in Caucasian but not in Asian populations . The putative role of the CYP19A1 gene in the development of AD has been investigated in several studies that yielded inconsistent results in Caucasians.…”

“…This finding is also consistent with a recent meta-analysis that found the rs2234693 was associated with risk of AD in Caucasian but not in Asian populations. 46 The putative role of the CYP19A1 gene in the development of AD has been investigated in several studies that yielded inconsistent results in Caucasians. A significant association was found between CYP19A1 and AD in a study with a small sample size, 28 whereas data from genome-wide association studies with larger sample sizes conducted in Canada 22 and the United States 47 have not found such an association.…”

ESR1 gene polymorphisms PvuII (rs2234693T>C) and XbaI (rs9340799A>G) may not be directly correlated with cardiovascular disease risk

“…Estrogen receptor 1 (ESR1) is an essential member of the nuclear hormone receptor super family and serves as a ligand-activated transcription factor composed of several domains important for DNA binding, hormone binding, and transcription activation (Cheng et al, 2014). ESR1 is mainly expressed in macrophages, endothelial cells, and vascular smooth muscle cells, and it plays an important role in vascular wall physiology and function (Gao et al, 2014).…”

Estrogen receptor-alpha gene XbaI A > G polymorphism influences short-term cognitive decline in healthy oldest-old individuals

“…Some hypotheses for the functional significance of this polymorphism shall be discussed. Cheng et al 14 reported that ERS-1 polymorphisms might influence the gene expression and affect estrogen function. Given its location, 351 bp upstream from the start of exon 2, a mechanism including changes on ESR-1 expression via altered binding of transcription factors and influence on alternative splicing of the ESR-1 gene has been suggested 15 .…”