Association of the WNT3 polymorphisms and non-syndromic cleft lip with or without cleft palate: evidence from a meta-analysis

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.