Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft.
Associations between microRNA binding site SNPs in FGFs and FGFRs and the risk of non-syndromic orofacial cleft.
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FGF 和 FGFR 中的 microRNA 结合位点 SNP 与非综合征性口面裂风险之间的关联
DOI：
10.1038/srep31054
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发表时间：
2016-08-11
影响因子：
4.6
通讯作者：
Pan Y
中科院分区：
文献类型：
--
作者：
Li D;Zhang H;Ma L;Han Y;Xu M;Wang Z;Jiang H;Zhang W;Wang L;Pan Y
我们假设成纤维细胞生长因子（FGF）及其受体基因（FGFR）中的microRNA结合位点单核苷酸多态性（SNP）可能影响microRNA和mRNA的相互作用，从而与非综合征性口面裂（NSOC）的易感性相关。在对602名NSOC患者和605名健康对照进行的病例对照研究中，选择了FGF和FGFR基因中的10个SNP，并研究了它们与NSOC易感性的相关性。FGF 2/rs 1048201、FGF 5/rs3733336和FGF 9/rs 546782与NSOC易感性提示相关。在联合分析中，观察到的比值比（OR）随着保护性等位基因（rs 1048201-T、rs3733336-G和rs 546782-T）的数量而降低，但在第一次比较后无统计学显著性。预测hsa-miRNA-496、hsa-miRNA-145和hsa-miRNA-187是在这些SNP内/附近具有结合位点的miRNA，并且在唇组织中表达。在用相应的miRNA转染的三个细胞系中观察到FGF 2、FGF 5和FGF 9表达降低。此外，在荧光素酶分析中，这三个SNP可能有助于hsa-miRNA-496与FGF 2、hsa-miRNA-145与FGF 5、hsa-miRNA-187与FGF 9之间的差异结合效力。结果表明，FGF 2/rs 1048201、FGF 5/rs3733336和FGF 9/rs 546782与NSOC的风险相关，并且这些miRNA-FGF相互作用可能影响NSOC的发展。
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.