中国人群心脏转录因子的单核苷酸多态性与先天性心脏病关系的Meta分析
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摘要
目的评价中国人群心脏转录因子(NKX2.5、GATA4、TBX5、FOG2)的单核苷酸多态性(SNP)与先天性心脏病(CHD)的关系。方法检索Pub Med、Google学术、中国知网、万方数据资源系统、重庆维普数据库等中英文数据库获取中国人群目标基因SNP与CHD关系的文献。当同一位点研究文献数≥2时,采用随机或固定效应模型将各研究结果合并,计算合并OR及95%CI。若位点只在单篇文献中提及,则提取文献相关数据计算该位点SNP与CHD的关系。结果共纳入23篇文献。Meta分析结果显示,GATA4中rs1139244和rs867858的基因型和等位基因频率及rs904018的基因型频率在CHD组和对照组中差异有统计学意义,未发现其余基因位点SNP在CHD组和对照组中差异有统计学意义。单篇文献分析结果显示,NKX2.5中rs118026695和rs703752、GATA4中rs884662、rs12825、rs12458、rs3203358、rs4841588及TBX5中rs6489956等位基因频率在两组中差异存在统计学意义。现有FOG2基因位点的SNP在两组中差异无统计学意义。结论中国人群NKX2.5、GATA4、TBX5基因的一些现有位点的SNP与CHD的发生有关;尚未发现FOG2基因现有位点的SNP与CHD的发生有关。
Objective To study the association of single nucleotide polymorphisms(SNPs) of transcription factors(NKX2.5, GATA4, TBX5, and FOG2) with congenital heart disease(CHD) in the Chinese population. Methods Pub Med, Google Scholar, CNKI, Wanfang Data, and Weipu Data were searched for articles on the association of SNPs of target genes with CHD in the Chinese population. If one locus was mentioned in at least two articles, the random or fixed effect model was used to perform a pooled analysis of study results and to calculate the pooled OR and its 95%CI. If a locus was mentioned in only one article, related data were extracted from this article to analyze the association between the SNPs of this locus and CHD. Results Twenty-three articles were included. The Meta analysis showed that there were significant differences between the CHD and control groups in the genotype and allele frequencies of GATA4 rs1139244 and rs867858 and the genotype frequency of GATA4 rs904018, while there were no significant differences in the SNPs of the other genetic loci between the two groups. The single-article analysis showed that there were significant differences between the two groups in the allele frequencies of NKX2.5 rs118026695/rs703752, GATA4 rs884662/rs12825/rs12458/rs3203358/rs4841588, and TBX5 rs6489956. There were no significant differences in the SNPs of FOG2 locus between the two groups. Conclusions The SNPs of some loci in NKX2.5, GATA4, and TBX5 are associated with CHD in the Chinese population, but the association between the SNPs of FOG2 locus and the development of CHD has not been found yet.
Objective To study the association of single nucleotide polymorphisms(SNPs) of transcription factors(NKX2.5, GATA4, TBX5, and FOG2) with congenital heart disease(CHD) in the Chinese population. Methods Pub Med, Google Scholar, CNKI, Wanfang Data, and Weipu Data were searched for articles on the association of SNPs of target genes with CHD in the Chinese population. If one locus was mentioned in at least two articles, the random or fixed effect model was used to perform a pooled analysis of study results and to calculate the pooled OR and its 95%CI. If a locus was mentioned in only one article, related data were extracted from this article to analyze the association between the SNPs of this locus and CHD. Results Twenty-three articles were included. The Meta analysis showed that there were significant differences between the CHD and control groups in the genotype and allele frequencies of GATA4 rs1139244 and rs867858 and the genotype frequency of GATA4 rs904018, while there were no significant differences in the SNPs of the other genetic loci between the two groups. The single-article analysis showed that there were significant differences between the two groups in the allele frequencies of NKX2.5 rs118026695/rs703752, GATA4 rs884662/rs12825/rs12458/rs3203358/rs4841588, and TBX5 rs6489956. There were no significant differences in the SNPs of FOG2 locus between the two groups. Conclusions The SNPs of some loci in NKX2.5, GATA4, and TBX5 are associated with CHD in the Chinese population, but the association between the SNPs of FOG2 locus and the development of CHD has not been found yet.
引文
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[24]李栋.?先天性心脏病血浆micro RNA表达谱及与GATA4靶序列单核苷酸多态性的关联研究[D].?济南:?山东大学,?2015.
[25]许细财,?李奋,?周万平,?等.?单纯性房间隔缺损患儿GATA4和GATA6基因突变筛查[J].?临床儿科杂志,?2015,?33(3):?225-229.
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[27]Cao Y,Wang J,Wei C,et al.Genetic variations of NKX2-5in sporadic atrial septal defect and ventricular septal defect in Chinese Yunnan population[J].Gene,2016,575(1):29-33.
[28]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.
[29]杨景晖,?许小艳,?米弘瑛,?等.?NKX2.5基因和TBX5基因在先天性心脏病试管婴儿中的突变检测[J].?中国当代儿科杂志,?2017,?19(6):?652-657.
[30]Sadowski SL.Congenital cardiac disease in the newborn infant:past,present,and future[J].Crit Care Nurs Clin North Am,2009,21(1):37-48.
[31]宫立国,?邱广蓉,?徐小延,?等.?心脏特异转录因子NKX2-5、TBX5、GATA4与先天性心脏病的研究进展[J].?国际遗传学杂志,?2006,?29(2):?133-136.
[32]李金,?唐燕华.?NKX2-5与先天性心脏病发病关系的研究进展[J].?中国循环杂志,?2014,?29(12):?1061-1063.
[33]Wang Z,Zou L,Zhong R,et al.Associations between two genetic variants in NKX2-5 and risk of congenital heart disease in Chinese population:a meta-analysis[J].PLo S One,2013,8(8):e70979.
[34]Zhang Y,Ai F,Zheng J,et al.Associations of GATA4 genetic mutations with the risk of congenital heart disease:a metaanalysis[J].Medicine(Baltimore),2017,96(18):e6857.
[35]胡易池,?杨毅宁.?NKX2.5和TBX5与先天性心脏病的研究进展[J].?医学综述,?2012,?18(13):?1986-1989.
[36]齐冰阳.?一个导致家族性房间隔缺损的新的GATA4基因突变[D].?长春:?吉林大学,?2017.
[37]许耘红,?何穗镕,?李丽青.?心肌转录因子和锌指转录因子在先天性心脏病中的相互作用[J].?中国临床药理学杂志,?2017,?33(18):?1773-1775.
[2]Knowles R,Griebsch I,Dezateux C,et al.Newborn screening for congenital heart defects:a systematic review and costeffectiveness analysis[J].Health Technol Assess,2005,9(44):1-152,iii-iv.
[3]蔡花,?付四清.?Nkx2.5基因与先天性心脏病[J].?中国优生与遗传杂志,?2014,?22(4):?1-3.
[4]刘敏,?赵洛沙.?先天性心脏病患者相关突变基因的筛选[J].?中华高血压杂志,?2015,?23(3):?758.
[5]Xie X,Shi X,Xun X,et al.Associations of NKX2-5 genetic polymorphisms with the risk of congenital heart disease:a meta analysis[J].Pediatr Cardiol,2016,37(5):953-961.
[6]Lo CK,Mertz D,Loeb M.Newcastle-Ottawa Scale:comparing reviewers'to authors'assessments[J].BMC Med Res Methodol,2014,14:45.
[7]石琳,?申阿东,?李晓峰,?等.?中国先天性心脏病Nkx2.5基因突变筛查及关联研究[J].?首都医科大学学报,?2005,?26(5):?525-528.
[8]周云.?转录因子GATA-4在人胎心发育中的表达及在先天性心脏病胎儿中的突变检测[D].?福州:?福建医科大学,?2007.
[9]Zhang W,Li X,Shen A,et al.Screening NKX2.5 mutation in a sample of 230 Han Chinese children with congenital heart diseases[J].Genet Test Mol Biomarkers,2009,13(2):159-162.
[10]刘兴元,?杨奕清,?杨颖,?等.?先天性室间隔缺损患者NKX2-5基因新突变的识别[J].?中华医学杂志,?2009,?89(34):?2395-2399.
[11]刘兴元,?杨奕清,?杨颖,?等.?房间隔缺损患儿NKX2.5基因突变的研究[J].?中华儿科杂志,?2009,?47(9):?696-700.
[12]Peng T,Wang L,Zhou SF,et al.Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease[J].Genetica,2010,138(11-12):1231-1240.
[13]李静.?GATA4基因多态性与中国西北人群室间隔缺损的关联研究[D].?兰州:?兰州大学,?2010.
[14]王娟,?胡大一,?李新明,?等.?先天性心脏病患者GATA4基因新突变的识别[J].?中华医学杂志,?2010,?90(10):?667-671.
[15]Ouyang P,Saarel E,Bai Y,et al.A de novo mutation in NKX2.5associated with atrial septal defects,ventricular noncompaction,syncope and sudden death[J].Clin Chim Acta,2011,412(1-2):170-175.
[16]韩增强,?唐胤,?陈彧,?等.?81例单纯性先天性心脏病患者NKx?2.5基因突变筛查及关联研究[J].?中国循环杂志,?2011,?26(6):?461-464.
[17]Pang S,Shan J,Qiao Y,et al.Genetic and functional analysis of the NKX2-5 gene promoter in patients with ventricular septal defects[J].Pediatr Cardiol,2012,33(8):1355-1361.
[18]王风.?mi RNAs对TBX5的靶向调控及其遗传变异的调控差异在先天性心脏病中的作用[D].?上海:?复旦大学,?2012.
[19]Xiong F,Li Q,Zhang C,et al.Analyses of GATA4,NKX2.5,and TFAP2B genes in subjects from southern China with sporadic congenital heart disease[J].Cardiovasc Pathol,2013,22(2):141-145.
[20]Huang X,Niu W,Zhang Z,et al.Identification of novel significant variants of ZFPM2/FOG2 in non-syndromic Tetralogy of Fallot and double outlet right ventricle in a Chinese Han population[J].Mol Biol Rep,2014,41(4):2671-2677.
[21]丁琰,?段君凯,?雷华平,?等.?先天性心脏病患者Nkx2.5基因突变研究[J].?医学信息,?2014,?27(6):?193-194.
[22]赵晓波.?单纯性先天性心脏病NKX2-5基因突变筛查及关联研究[D].?武汉:?华中科技大学,?2014.
[23]Yang XY,Jing XY,Chen Z,et al.Correlation between GATA4gene polymorphism and congenital heart disease[J].Int J Clin Exp Med,2015,8(9):16733-16736.
[24]李栋.?先天性心脏病血浆micro RNA表达谱及与GATA4靶序列单核苷酸多态性的关联研究[D].?济南:?山东大学,?2015.
[25]许细财,?李奋,?周万平,?等.?单纯性房间隔缺损患儿GATA4和GATA6基因突变筛查[J].?临床儿科杂志,?2015,?33(3):?225-229.
[26]尤涛,?丁兆红,?刘兴光,?等.?GATA4基因多态性与先天性心脏病相关性研究[J].?兰州大学学报(医学版),?2015,?41(1):?60-62.
[27]Cao Y,Wang J,Wei C,et al.Genetic variations of NKX2-5in sporadic atrial septal defect and ventricular septal defect in Chinese Yunnan population[J].Gene,2016,575(1):29-33.
[28]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.
[29]杨景晖,?许小艳,?米弘瑛,?等.?NKX2.5基因和TBX5基因在先天性心脏病试管婴儿中的突变检测[J].?中国当代儿科杂志,?2017,?19(6):?652-657.
[30]Sadowski SL.Congenital cardiac disease in the newborn infant:past,present,and future[J].Crit Care Nurs Clin North Am,2009,21(1):37-48.
[31]宫立国,?邱广蓉,?徐小延,?等.?心脏特异转录因子NKX2-5、TBX5、GATA4与先天性心脏病的研究进展[J].?国际遗传学杂志,?2006,?29(2):?133-136.
[32]李金,?唐燕华.?NKX2-5与先天性心脏病发病关系的研究进展[J].?中国循环杂志,?2014,?29(12):?1061-1063.
[33]Wang Z,Zou L,Zhong R,et al.Associations between two genetic variants in NKX2-5 and risk of congenital heart disease in Chinese population:a meta-analysis[J].PLo S One,2013,8(8):e70979.
[34]Zhang Y,Ai F,Zheng J,et al.Associations of GATA4 genetic mutations with the risk of congenital heart disease:a metaanalysis[J].Medicine(Baltimore),2017,96(18):e6857.
[35]胡易池,?杨毅宁.?NKX2.5和TBX5与先天性心脏病的研究进展[J].?医学综述,?2012,?18(13):?1986-1989.
[36]齐冰阳.?一个导致家族性房间隔缺损的新的GATA4基因突变[D].?长春:?吉林大学,?2017.
[37]许耘红,?何穗镕,?李丽青.?心肌转录因子和锌指转录因子在先天性心脏病中的相互作用[J].?中国临床药理学杂志,?2017,?33(18):?1773-1775.