A systematic review and meta-analysis on protective role of forkhead box E1 (FOXE1) polymorphisms in susceptibility to non-syndromic cleft lip/palate

Introduction: Several environmental and genetic factors have a role in the aetiology of non-syndromic cleft lip/palate (NSCL/P). This meta-analysis evaluated the association of rs3758249 and rs4460498 forkhead box E1 (FOXE1) polymorphisms with the NSCL/P risk.

Materials and methods: The Scopus, Cochrane Library, Web of Science, and PubMed databases were searched for articles published until March 2019. The analyses were performed by Review Manager 5.3 using the crude odds ratio (OR) and 95% confidence interval (CI) for a strong association between FOXE1 polymorphisms and the risk of NSCL/P.

Results: Out of 161 articles retrieved from the databases, four case-control articles were involved in the meta-analysis. The pooled ORs of rs4460498 polymorphism based on allelic, homozygous, heterozygous, dominant, and recessive models were 0.74 (95% CI: 0.69, 0.80; P<0.00001), 0.43 (95% CI: 0.30, 0.61; P<0.00001), 0.66 (95% CI: 0.55, 0.80; P<0.0001), 0.66 (95% CI: 0.59, 0.73; P<0.00001), and 0.70 (95% CI: 0.60, 0.82; P<0.0001), respectively; whereas, the pooled OR of rs3758249 polymorphism were 0.86 (95% CI: 0.71, 1.04; P=0.12), 0.68 (95% CI: 0.57, 0.82; P<0.0001), 0.79 (95% CI: 0.57, 1.09; P=0.15), 0.79 (95% CI: 0.58, 1.08; P=0.14), and 0.80 (95% CI: 0.68, 0.95; P=0.010) for the afore-mentioned models, respectively.

Conclusions: The results showed that the T allele, TT, and CT genotypes of rs4460498 polymorphism were significantly associated with a decreased risk of NSCL/P; whereas, for rs3758249 polymorphism, only the AA genotype had a significant protective role in NSCL/P. Thus, FOXE1 is strongly associated with NSCL/P in the populations.