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We hypothesized that microRNA binding site single nucleotide polymorphisms (SNPs) in fibroblast growth factors ( FGFs ) and their receptor genes ( FGFRs ) may affect microRNA and mRNA interactions and are thereby associated with susceptibility of non-syndromic orofacial cleft (NSOC). Ten SNPs among the  FGF  and  FGFR  genes were selected and their associations with NSOC susceptibility were investigated in a case-control study of 602 patients with NSOC and 605 healthy controls.  FGF2 /rs1048201,  FGF5 /rs3733336 and  FGF9 /rs546782 showed suggestive association with NSOC susceptibility. In the combination analysis, the observed odds ratios (ORs) decreased with the number of protective alleles (rs1048201-T, rs3733336-G and rs546782-T) but were not statistically significant beyond the first comparison. Hsa-miRNA-496, hsa-miRNA-145 and hsa-miRNA-187 were predicted to be miRNAs with binding sites within/near these SNPs and were expressed in lip tissues. Decreased  FGF2 ,  FGF5  and  FGF9  expression was observed in three cell lines transfected with the corresponding miRNAs. Moreover, the three SNPs could contribute to differential binding efficacy between hsa-miRNA-496 and  FGF2 , hsa-miRNA-145 and  FGF5 , hsa-miRNA-187 and  FGF9  in luciferase assay. The results suggest that  FGF2 /rs1048201,  FGF5 /rs3733336 and  FGF9 /rs546782 are associated with the risk of NSOC and that these miRNA- FGF  interactions may affect NSOC development.

Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft