Association between the estrogen receptor α gene polymorphisms rs2234693 and rs9340799 and severe and mild pre-eclampsia: a meta-analysis

This meta-analysis was performed in order to determine the associations between the estrogen receptor α (ESR1) gene PvuII site (-397T/C, rs2234693) and XbaI site (-351A/G, rs9340799) polymorphisms with severe and mild pre-eclampsia. Eligible studies were identified by searching PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and WanFang databases until May 2018. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate the associations. Six articles (consisting of seven studies; one article was considered as two separate studies with two different subpopulations) investigated the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms in severe and mild pre-eclampsia patients and included controls. The pooled results indicated an increased risk of severe pre-eclampsia for the XbaI -351A/G polymorphism (OR = 1.67, 95% CI = 1.10–2.25, P=0.017 for GG compared with AA+GA; OR = 1.81, 95% CI = 1.17–2.82, P=0.008 for GG compared with GA). The GG genotype of the ESR1 XbaI polymorphism could be a genetic risk factor for severe pre-eclampsia susceptibility. However, the ESR1 gene PvuII -397T/C polymorphism was not significantly associated with the risk of severe pre-eclampsia, and there was no association between mild pre-eclampsia and the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms separately. The current meta-analysis indicates that the ESR1 XbaI genetic polymorphism may be associated with severe pre-eclampsia. However, there was no association of the ESR1 gene PvuII and XbaI polymorphisms with the risk of mild pre-eclampsia. Owing to the low statistical power, the results may not be sufficiently robust and this conclusion should be interpreted cautiously, which highlights the requirement for large-scale and high-quality studies in this field.

DNA Methylation Status of the Estrogen Receptor α Gene in Canine Mammary Tumors

Estrogen receptor α (ERα) has an important role in mammary carcinogenesis, prognosis, and treatment. In human and canine mammary cancer, the most aggressive tumors show loss of ERα expression, which in human breast cancer has been attributed to methylation of the cytosine followed by guanine (CpG) island within the estrogen receptor α gene ( ESR1) promoter. This study aimed to investigate the role of ESR1 CpG island (CGI) methylation in ERα expression in canine mammary tumors. Twenty-one canine mammary samples were sorted into three groups: malignant tumor (n = 9), benign tumor (n = 8), and normal gland (n = 4). Immunohistochemical analysis and reverse-transcription quantitative real-time PCR were performed to assess ERα expression and ESR1 mRNA levels. The methylation status was determined using sodium-bisulfite-treated DNA sequencing. All normal mammary glands and benign tumors showed high ERα expression (score range, 5–8). Six of the nine malignant tumors did not show ERα expression (score 0), two had score 2, and one had score 4. Lower ERα ( P < .005) and ESR1 mRNA levels ( P < .005) were found in malignant mammary tumors than in the other two groups. Canine ESR1 has an intragenic and non-promoter-associated CGI, different from humans. No significant variation in methylation percentage was observed among the groups, suggesting that ESR1 is not regulated by DNA methylation, unlike that in humans. This difference should be considered in further research using ERα as a biomarker for mammary tumors in canine studies on ERα-targeting therapy.