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

Abstract

The purpose of the present work was to investigate the association between forkhead box E1 (FOXE1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). Relevant studies were searched in several professional databases up to July 31, 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 analyze the relationship between FOXE1 polymorphisms and NSCL/P. A total of four single nucleotide polymorphisms (SNPs), including rs3758249, rs4460498, rs1443434, and rs10217225, were analyzed. 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= 0.000; TT vs TC+CC, OR = 0.775, P= 0.020; CL/P: TT vs CC, OR = 0.664, P= 0.000; TT vs TC+CC, OR = 0.738, P= 0.006. CPO: TT vs CC, OR = 0.761, P= 0.027; TT vs TC+CC, OR = 0.792, P= 0.045). For rs10217225, only the TT genotype might have contributed to the elevated risk of CL/P (TT vs CC OR=2.236, P=0.000). The other FOXE1 polymorphisms were not associated with NSCLP, CL/P, or CPO. 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.