Abstract
Objective: This meta-analysis was conducted with the aim of investigating the association between WNT3 gene polymorphisms and non-syndromic cleft lip (CL) with or without cleft palate (NSCL/P) predisposition. Methods: A comprehensive literature search was performed in six online databases including PubMed, Embase, ISI Web of Science, CENTRAL, CNKI, and Wanfang from inception up to June 2018 without language restriction. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated under allele model of inheritance to indicate the association between WNT3 polymorphisms and NSCL/P. Risk of bias was assessed through the Newcastle–Ottawa scale (NOS). Predetermined stratified and sensitivity analyses were performed using the RevMan 5.3 software, publication bias were evaluated by Egger’s and Begg’s tests. Results: Seven case–control studies comprising 1617 NSCL/P patients and 2143 healthy controls were identified and included in the present study, a total of eight loci were investigated in the present study: rs3809857 was significantly associated with NSCL/P vulnerability (G compared with T, OR = 1.34, 95%CI: 1.15–1.56, P=0.0001), a significant association between rs9890413 polymorphism and NSCL/P susceptibility (A compared with G, OR = 1.25, 95%CI: 1.06–1.47, P=0.007) was detected as well. Since only few studies reported detailed data about the association between rs142167, rs7207916, rs199498, rs111769, rs12452064, rs11653738, and NSCL/P risk, these results were not combined using meta-analysis. Conclusion: Based on the findings of our current study, the rs3809857 and rs9890413 polymorphisms of WNT3 appeared to be associated with NSCL/P. Limited evidence is found to support the association between other WNT3 polymorphisms and risk of NSCL/P.
Highlights
Non-syndromic cleft lip (CL) with or without cleft palate (NSCL/P) is one of the most frequent congenital malformation amongst live births worldwide
As far as we know, NSF is involved in intracellular protein transport, but the impact of NSF polymorphisms on NSCL/P has not yet been confirmed. Both rs3809857 and rs9890413 have regulatory motifs changed, and both the variants are associated with altered expression of WNT3 in human organs, which could be one of the reasons why these polymorphisms confer risk of NSCL/P
More evidence is needed to uncover the association between WNT3 polymorphisms and NSCL/P risk, based on the results of our meta-analysis we did find some genetic variants in WNT3 gene that possibly contribute to the risk of NSCL/P
Summary
Non-syndromic cleft lip (CL) with or without cleft palate (NSCL/P) is one of the most frequent congenital malformation amongst live births worldwide. The global prevalence of NSCL/P ranging from 1:500 to 1:2500 live births, with considerable variability across geographic origin, ethnic and racial background, as well as socioeconomic status [1]. NSCL/P can be generally divided into CL, cleft palate (CP), and CL and palate (CLP) [2]. A long term follow-up study has reported that NSCL/P is significantly correlated with increased risk of overall and cause specific mortality [3]. Advanced surgical treatment and rehabilitation have enabled sufferers to normal life, NSCL/P inevitably imposes a heavy burden on both family and society [4]
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