Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis.

Wenlei Yang, Yingnan Guo, Wenli Ni, Tian Tian, Lei Jin, Jufen Liu, Zhiwen Li, Aiguo Ren, Linlin Wang

Ecotoxicology and environmental safety 2021 Jan 15

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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. 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. 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. 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. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Wenlei Yang, Yingnan Guo, Wenli Ni, Tian Tian, Lei Jin, Jufen Liu, Zhiwen Li, Aiguo Ren, Linlin Wang. Hypermethylation of WNT3A gene and non-syndromic cleft lip and/or palate in association with in utero exposure to lead: A mediation analysis. Ecotoxicology and environmental safety. 2021 Jan 15;208:111415