COL6A2基因3′-UTR区域功能单核苷酸多态性位点rs1044598参与miR-4252调节中国汉族人群先天性房间隔缺损
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

国家自然科学基金(81300128, 81573234);江苏省自然科学基金(BK20131025);教育部博士点基金(20123234120015);教育部留学回国人员基金(FD12);新疆科技厅科技援疆专项(201391121)


The mechanism of miR-4252 regulating pathogenesis of congenital atrial septal defect with SNP (rs1044598) in 3′-UTR of COL6A2 in Han Chinese populations
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:探讨COL6A2基因3′非翻译区(3′-UTR)单核苷酸多态性(single nucleotide polymorphism,SNP)位点对先天性房间隔缺损(congenital atrial septal defect,ASD)发病风险的影响及其可能的作用机制。方法:搜索PubMed及Hapmap数据库获得COL6A2基因3′-UTR区域中国汉族人群最小等位基因频率>0.05的SNP位点,随后通过miRNA-SNP功能网站预测SNP位点的功能情况并与本课题组前期ASD全基因组关联研究数据库比对,研究SNP位点与ASD的发病关联,最后对可能的功能位点进行功能学研究。结果:rs1044598位点AA基因型较野生TT基因型显著减少了36%的患病风险。HEK293T细胞-H9C2细胞以及SD乳鼠原代心肌细胞荧光素酶报告基因转染实验证实,miR-4252与COL6A2基因rs1044598不同基因型表达质粒共转染后,荧光强度在3个细胞系中均有显著差异 (P < 0.05)。结论:COL6A2基因rs1044598位点的变异可能与ASD的发病风险相关。miR-4252可通过与COL6A2的3′-UTR区域发生有效结合而下调基因的表达,而rs1044598位点的变异参与这一机制并减少ASD的发生。

    Abstract:

    Objective:To investigate the association and potential mechanism between single nucleotide polymorphism (SNP)in 3′untranslated region(3′-UTR) of COL6A2 and the risk of congenital atrial septal defect(ASD). Methods:SNPs in 3′-UTR of COL6A2 were searched in PubMed and Hapmap database for minimum allele frequency (MAF)>0.05 in Han Chinese population. Then the potential functional SNPs were predicted in website of miRNA-SNP. Meanwhile,the association between SNPs and the risk of ASD was checked in our previous Genome-wide association study (GWAS) database of congenital septation defects. Results:Rs1044598 mutant genotype AA decreased the risk of ASD by 36% compared with wild genotype TT. The luciferase reporter assay further confirmed that the significant differences were detected in cotransfected plasmid (rs1044598) with miR-4252 in HEK293T,H9C2 and cardiac cells from newborn SD rats cell lines(all P < 0.05). Conclusion:Rs1044598 may be a new independent susceptibility locus of ASD. MiR-4252 down-regulates COL6A2 expression by binding to 3′-UTR of COL6A2,and rs1044598 could influence the procedure and decrease the risk of ASD.

    参考文献
    相似文献
    引证文献
引用本文

杨骏艺,许 晶,徐骁晗,王屹丰,林 苑,王晓伟. COL6A2基因3′-UTR区域功能单核苷酸多态性位点rs1044598参与miR-4252调节中国汉族人群先天性房间隔缺损[J].南京医科大学学报(自然科学版),2016,(9):1057-1062

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2016-04-23
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: 2016-09-18
  • 出版日期:
通知关闭
郑重声明