FOXE1 polymorphisms and non-syndromic orofacial cleft susceptibility in a Chinese Han population

Objective: FOXE1 plays an important role in craniofacial development. The aim of this study was to investigate associations between genetic variants of FOXE1 and risk of non-syndromic orofacial clefts in a Chinese population.

Materials and methods: Three potentially functional SNPs of FOXE1 (rs3758250 and rs907577 in the 5' upstream and rs7043516 in the 3'-UTR) were selected and their associations with non-syndromic orofacial cleft susceptibility were investigated in a case-control study from a Chinese population (602 cases and 605 controls). Genotyping was performed with double ligation and multiplex fluorescence PCR. Associations between the SNPs and risk of non-syndromic orofacial clefts and its subgroups were estimated from unconditional logistic regression analysis. Luciferase reporter assay was conducted to assess SNP function.

Results: Overall, we did not find any of the individual SNP or haplotype was associated with NSOC susceptibility. Nevertheless, in stratified analysis, we found rs7043516, locating in the 3'-UTR of FOXE1, was associated with risk of cleft lip only. Further in vitro luciferase assay indicated that this SNP could contribute to differential binding ability with miRNA.

Conclusions: Taken together, this study showed that rs7043516 may be considered as a potentially susceptible marker of cleft lip only among Chinese Han populations.