miR-583和miR-222-3p介导的GATA4靶序列SNP与先天性心脏病的关联研究
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摘要
目的探讨GATA4 3'UTR区miR-583和miR-222-3p靶序列SNPs与先心病的关联。方法应用生物信息数据库筛选功能性SNPs位点及参与调控的microRNA,分析microRNA与靶位点不同等位基因的结合情况并采用病例-对照研究进行靶位点SNPs与先心病的关联分析。结果 rs3203358位点等位基因C而非等位基因G能与miR-583结合;rs3203358 C﹥G位点等位基因或基因型在人群中分布频率差异存在统计学意义;G是先心病的保护等位基因,G/C和G/G为先心病的保护基因型。rs1062270位点G等位基因和A等位基因都能够与miR-222-3p结合且rs1062270 G>A等位基因或基因型频率与先心病易感性无关;突变等位基因A非先心病的保护性等位基因;G/A基因型者与G/G基因型者患先心病的风险不存在统计学差异。结论 rs3203358位点SNP与先心病遗传易感性有关,该位点C>G的突变会影响miR-583对GATA4的调控,改变先心病的易感性;rs1062270位点SNP与先心病易感性无关,miR-222-3p对GATA4基因转录活性的调控可能不依赖于碱基G>A的突变,也可能与microRNA自身的SNPs或microRNA合成通路相关基因的SNPs有关。
Objective To investigate the association between SNPs of miR-583 and miR-222-3 p target sequences in GATA4 3'UTR region and congenital heart disease.Methods The bioinformatics database was used to screen functional SNPs and microRNAs involved in regulation,and the binding of microRNAs to different alleles of target sites was analyzed.Case-control studies were used to analyze the association between target site SNPs and congenital heart disease.Results The rs3203358 allele C could bind to miR-583,and the allele G could not.rs3203358 C>G locus allele or genotype had a statistically significant difference in the frequency of distribution.G was a protective allele of congenital heart disease,and G/C and G/G were protective genotypes of it.Both the G allele and the A allele of the rs1062270 locus could bind to miR-222-3 p and the rs1062270 G>A allele or genotype frequency was not related to congenital susceptibility.The Allele A was not a protective one for congenital heart disease and there was no statistically significant difference in the risk of congenital heart disease between G/A genotype and G/G genotype.Conclusion The rs3203358 polymorphism is associated with the genetic susceptibility of congenital heart disease.The mutation of C>G in this locus can affect the regulation of GATA4 by miR-583 and change the susceptibility of congenital heart disease.The rs1062270 locus SNP s have nothing to do with the susceptibility of congenital heart disease.The regulation of GATA4 gene transcriptional activity by miR-222-3 p may not depend on the mutation of base G>A,or may be related to the SNPs of microRNA or microRNA synthesis pathway-related genes.
Objective To investigate the association between SNPs of miR-583 and miR-222-3 p target sequences in GATA4 3'UTR region and congenital heart disease.Methods The bioinformatics database was used to screen functional SNPs and microRNAs involved in regulation,and the binding of microRNAs to different alleles of target sites was analyzed.Case-control studies were used to analyze the association between target site SNPs and congenital heart disease.Results The rs3203358 allele C could bind to miR-583,and the allele G could not.rs3203358 C>G locus allele or genotype had a statistically significant difference in the frequency of distribution.G was a protective allele of congenital heart disease,and G/C and G/G were protective genotypes of it.Both the G allele and the A allele of the rs1062270 locus could bind to miR-222-3 p and the rs1062270 G>A allele or genotype frequency was not related to congenital susceptibility.The Allele A was not a protective one for congenital heart disease and there was no statistically significant difference in the risk of congenital heart disease between G/A genotype and G/G genotype.Conclusion The rs3203358 polymorphism is associated with the genetic susceptibility of congenital heart disease.The mutation of C>G in this locus can affect the regulation of GATA4 by miR-583 and change the susceptibility of congenital heart disease.The rs1062270 locus SNP s have nothing to do with the susceptibility of congenital heart disease.The regulation of GATA4 gene transcriptional activity by miR-222-3 p may not depend on the mutation of base G>A,or may be related to the SNPs of microRNA or microRNA synthesis pathway-related genes.
引文
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[2] 赵雷,关添允,赵佳怡,等.MicroRNA在心血管疾病中的研究进展[J].中国实验诊断学,2018,22(9):1659-1661.
[3] 尤雯丽,艾儒棣,陈明岭.健脾滋肾法联合西药治疗系统性红斑狼疮对患者血浆microRNA的影响[J].中华中医药杂志,2018,33(8):3644-3647.
[4] Zhang YP,Zhang WH,Dong MQ.The miR-58 microRNA family is regulated by insulin signaling and contributes to lifespan regulation in Caenorhabditis elegans[J].Science China.Life sciences,2018,61(9):1060-1070.
[5] 余章斌,韩树萍,郭锡熔.与心脏发育相关的miRNA研究[J].医学分子生物学杂志,2010,7(1):66-69.
[6] Gruber PJ.Cardiac development:new concepts[J].Clinics in Perinatology,2005,32(4):845-855.
[7] Burch JB.Regulation of GATA gene expression during vertebrate development[J].Seminars in Cell & Developmental Biology,2005,16(1):71-81.
[8] Ryan BM,Robles AI,Harris CC.Genetic variation in microRNA networks:the implications for cancer research[J].Nature Reviews Cancer,2010,10(6):389-402.
[9] 张丹,杨少萍,张斌,等.武汉市新生儿先天性心脏病的筛查与随访资料分析[J].中国妇幼保健,2018,33(16):3749-3752.
[10] 王晓玲.2012-2016年南京市鼓楼区围产儿先天性心脏病发生率及变化趋势分析[J].现代预防医学,2018,45(13):2346-2349.
[11] Kikuchi K,Holdway JE,Werdich AA,et al.Primary contribution to zebrafish heart regeneration by gata4(+)cardiomyocytes[J].Nature,2010,464(7288):601-U162.
[12] 黄雄.NKX2-5、TBX5和GATA4基因多态性与广西壮、汉族人群先天性心脏病关系及其功能验证[D].南宁:广西医科大学,2016.