Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis
Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis
复制标题
WNT3A 基因的高甲基化和非综合征性唇裂和/或腭裂与子宫内铅暴露相关：一项中介分析。
DOI：
10.1016/j.ecoenv.2020.111415
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发表时间：
2021-01-15
影响因子：
6.8
通讯作者：
Wang, Linlin
中科院分区：
文献类型：
--
作者：
Yang, Wenlei;Guo, Yingnan;Wang, Linlin
目的：本研究旨在探讨WNT 3A基因甲基化与非综合征性唇腭裂（NSCL/P）发病风险之间的关系，并探讨WNT 3A基因甲基化对NSCL/P与胎儿铅（Pb）暴露相关性的介导作用。中介分析，以评估潜在的介导作用的WNT 3A甲基化之间的关联在脐带中的铅浓度和风险为NSCL/P。此外，在腭裂的动物实验中，由醋酸铅诱导centered.Results：WNT 3A的整体平均甲基化水平是显着高于NSCL/P的情况下，与对照组相比。NSCL/P的风险随着WNT 3A的高甲基化而增加1.90倍。脐带血铅浓度与WNT 3A甲基化水平呈显著相关。WNT 3A基因甲基化在铅对NSCL/P的影响中起中介作用，其作用占铅对NSCL/P总影响的9.32%。在男性胎儿中观察到WNT 3A甲基化与NSCL/P的性别特异性关联，并且介导效应的百分比增加至14.28%。结论：WNT 3A基因甲基化与NSCL/P的发病风险相关，可能是铅暴露与NSCL/P发病风险相关的部分原因。
Objectives: We aim to investigate association between WNT3A methylation and risk of non-syndromic cleft lip and/or palate (NSCL/P), and examine mediating effect of WNT3A methylation on the association of NSCL/P and lead (Pb) exposure in fetuses.Methods: DNA methylation of WNT3A in umbilical cord blood was determined among 59 NSCL/P cases and 118 non-malformed controls. Mediation analysis was performed to evaluate the potential mediating effect of WNT3A methylation on association between concentrations of Pb in umbilical cord and risk for NSCL/P. Additionally, an animal experiment in which cleft palates were induced by lead acetate was conducted.Results: The overall average methylation level of WNT3A was significant higher in NSCL/P cases as compared to controls. The risk for NSCL/P was increased by 1.90-fold with hypermethylation of WNT3A. Significant correlation was observed between concentrations of Pb in umbilical cord and methylation level of WNT3A. The hypermethylation of WNT3A had a mediating effect by 9.32% of total effect of Pb on NSCL/P risk. Gender specific association between WNT3A methylation and NSCL/P was observed in male fetuses, and the percentage of the mediating effect increased to 14.28%. Animal experiment of mice showed that maternal oral exposure to lead acetate may result in cleft palate in offspring.Conclusion: Hypermethylation of WNT3A was associated with the risk for NSCL/P and may be partly explain the association between exposure to Pb and risk for NSCL/P. The teratogenic and fetotoxic effects of Pb were found in mice.