title: Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft.
abstract: 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.
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Dandan
authors: D
authors: Li
authors: Xuzhou First People's Hospital, Xuzhou, 221000, China.
authors: Hongchuang
authors: H
authors: Zhang
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Lan
authors: L
authors: Ma
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Yue
authors: Y
authors: Han
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Min
authors: M
authors: Xu
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Zhendong
authors: Z
authors: Wang
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Hongbing
authors: H
authors: Jiang
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Weibing
authors: W
authors: Zhang
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Lin
authors: L
authors: Wang
authors: Institute of Stomatology, Nanjing Medical University, Nanjing, 210029, China.|Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China.
authors: Yongchu
authors: Y
authors: Pan
mesh_terms: D001665:Binding Sites / Q000235:genetics; D001921:Brain / Q000002:abnormalities*; D016022:Case-Control Studies; D002971:Cleft Lip / Q000453:epidemiology / Q000235:genetics*; D002972:Cleft Palate / Q000453:epidemiology / Q000235:genetics*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D051521:Fibroblast Growth Factor 5 / Q000235:genetics*; D051525:Fibroblast Growth Factor 9 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment
chemical_list: C496449:FGF5 protein, human; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D035683:MicroRNAs; D016222:Fibroblast Growth Factor 2; D051521:Fibroblast Growth Factor 5