A functional polymorphism in the pre-miR-146a gene is associated with the risk of nonsyndromic orofacial cleft
A functional polymorphism in the pre-miR-146a gene is associated with the risk of nonsyndromic orofacial cleft
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pre-miR-146a 基因的功能多态性与非综合征性口面裂的风险相关
DOI：
10.1002/humu.23415
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发表时间：
2018-05-01
期刊：
影响因子：
3.9
通讯作者：
Wang, Lin
中科院分区：
文献类型：
--
作者：
Pan, Yongchu;Li, Dandan;Wang, Lin
microRNAs （miRNAs）广泛参与颅面发育，miRNAs的遗传变异可能与非综合征性口面裂（NSOC）的风险相关。在这里，我们系统地选择了mirna的5个单核苷酸多态性（snp），并在一项两期病例对照研究中研究了这些变异与NSOC易感性之间的关系，该研究包括来自中国人群的1,406名NSOC患者和1,578名对照。我们发现，与C等位基因相比，pre-miR-146a的rs2910164 G等位基因与NSOC风险增加相关（加性模型：优势比[OR]=1.17, 95%可信区间[CI]: 1.06-1.30， P=0.002），包括唇裂伴或不伴腭裂（CL/P）和单纯腭裂（CPO）。生物信息学预测和功能分析显示，rs2910164的C等位基因与抑制HEK-293和HEPM细胞增殖和降低TRAF6丰度显著相关。miR-146a和TRAF6在NSOC患者的唇组织样本中均有表达，两者之间呈中度负相关。综上所述，这些结果表明miR-146a/rs2910164与NSOC易感性相关，为NSOC的遗传病因学和潜在生物学提供了新的见解。
microRNAs (miRNAs) are widely involved in craniofacial development, and genetic variants of miRNAs may be associated with the risk of nonsyndromic orofacial cleft (NSOC). Here, we systematically selected five single nucleotide polymorphisms (SNPs) of miRNAs and investigated the associations between these variants and NSOC susceptibility in a two-stage case-control study including 1,406 NSOC patients and 1,578 controls from the Chinese population. We found that compared with the C allele, the rs2910164 G allele of pre-miR-146a was associated with an increased risk of NSOC (additive model: odds ratio [OR]=1.17, 95% confidence interval [CI]: 1.06-1.30, P=0.002), including both cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO). Bioinformatic prediction and functional assays revealed that the C allele of rs2910164 was significantly associated with inhibited HEK-293 and HEPM cell proliferation and decreased abundance of TRAF6. Both miR-146a and TRAF6 were expressed in the lip tissue samples of NSOC patients, and a moderate inverse correlation was observed between them. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to NSOC, providing novel insights into the genetic etiology and underlying biology of NSOC.