Association between forkhead box E1 polymorphisms and risk of non-syndromic cleft lip with or without cleft palate: A meta-analysis

Objective The purpose of the present work was to investigate the association between forkhead box E1 (FOXE1) and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Materials and Methods Relevant studies were searched in several professional databases up to 31 July 2019. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effect model or a random-effect model to analyse the relationship between FOXE1 polymorphisms and NSCL/P. Results A total of four single nucleotide polymorphisms (SNPs), including rs3758249, rs4460498, rs1443434 and rs10217225, were analysed. The overall findings showed that FOXE1 rs4460498 was statistically associated with NSCL/P (including cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO)). Genotypes CC and CT of rs4460498 were significantly more closely correlated with NSCL/P (including CL/P and CPO) than genotype TT (NSCL/P: TT vs CC, OR = 0.630, P = .000; TT vs TC + CC, OR = 0.775, P = .020; CL/P: TT vs CC, OR = 0.664, P = .000; TT vs TC + CC, OR = 0.738, P = .006. CPO: TT vs CC, OR = 0.761, P = .027; TT vs TC + CC, OR = 0.792, P = .045). For rs10217225, only the TT genotype might have contributed to the elevated risk of CL/P (TT vs CC OR = 2.236, P = .000). The other FOXE1 polymorphisms were not associated with NSCLP, CL/P or CPO. Conclusion The meta-analysis provided confirmation that the polymorphism of FOXE1 rs10217225 was correlated with an increased risk of CL/P, and the polymorphism of FOXE1 rs4460498 was a protective factor for NSCL/P, including CLP and CPO.