调控microRNA成熟的通路基因标签单核苷酸多态性与原发性肝癌易感性的关系
조공microRNA성숙적통로기인표첨단핵감산다태성여원발성간암역감성적관계
Correlation between tag single nucleotide polymorphisms of microRNA regulatory genes and the gentic susceptibility of primary liver cancer
  • 万方数据
    中华预防医学杂志 중화예방의학잡지
    CHINESE JOURNAL OF
    2012年 6期 533-537 ,共5页

    李玉春%宋春花%杨文杰%代丽萍%王鹏%史健翔%张建营%王凯娟

    리옥춘%송춘화%양문걸%대려평%왕붕%사건상%장건영%왕개연

    微RNAs%多态性,单核苷酸%肝肿瘤%疾病遗传易感性 微RNAs%多態性,單覈苷痠%肝腫瘤%疾病遺傳易感性
    미RNAs%다태성,단핵감산%간종류%질병유전역감성
    MicroRNAs%Polymorphism,single nucleotide%Liver neoplasms%Genetic predisposition to disease
    目的 研究调控microRNA成熟的通路基因(DICERI、RAN及GEMIN4基因)标签单核苷酸多态性(tSNP)与原发性肝癌遗传易感性的相关性.方法 采用1∶1配对病例-对照研究,将2008年9月至2010年12月在郑州某两个教学医院就诊的532例原发性肝癌患者纳入病例组,将532名健康个体纳入对照组,对其进行面对面调查并采集外周静脉血5ml.从DICER1、RAN及GEMIN4基因中筛选tSNP,采用PCR-RFLP或等位基因特异PCR技术对研究对象进行基因分型,应用多因素条件logistic回归及多因素降维法(MDR)分析tSNP与原发性肝癌易感性的关系及其与环境因素的交互作用.结果 在所筛选的DICER1、RAN及GEMIN4基因tSNP中,rs14035位点CC、CT、TT基因型在病例组中的频率分别为67.29％ (358/532)、28.20％ (150/532) 、4.51％ (24/532),在对照组的频率分别为70.30％(374/532)、28.20％ (150/532)、1.50％( 8/532)(x2=8.35,P ＜0.05)；rs1045491位点GG、GA、AA基因型在病例组中的频率分别为71.05％ (378/532)、26.69％( 142/532)、2.26％(12/532),在对照组的频率分别为80.45％(428/532)、18.42％(98/532)、1.13％(6/532)(x2 =13.17,P＜0.01)；rs2291778位点GG、GT、TT基因型在病例组中的频率分别为53.38％( 284/532)、40.23％(214/532)、6.39％( 34/532),在对照组的频率分别为25.94％ (138/532)、63.91％(340/532)、10.15％( 54/532)(x2=83.71,P＜0.01).rs14035位点TT基因型(OR=2.54,95％CI:1.19 ～6.32)、rs1045491位点GA基因型(OR=1.74,95％CI:1.08 ～2.66)是原发性肝癌的易感基因型,rs2291778位点的GT基因型(OR =0.52,95％ CI:0.43～0.75)和TT基因型(OR=0.62,95％CI:0.46 ～0.86)是原发性肝癌的非易感基因型.单体型分析显示,单体型3 (AACTGGGT)(OR=1.42,95％CI:1.10～1.82)和单体型5(AGCCAGCC)( OR=1.36,95％ CI:1.02～1.80)可增加肝癌发病风险,而单体型2( AACTATCC)(OR=0.69,95％CI:0.52 ～0.91)和单体型6(AACTGTGT)(OR =0.61,95％ CI:0.45～0.81)可降低原发性肝癌发病风险.具有rs1045491(等位基因A)、rs14035(等位基因T)和HBV感染的交互组合的人群是原发性肝癌的高发人群(OR=3.72,95％ CI:2.38～ 5.56).结论 rs14035位点TT基因型、rs1045491位点GA基因型是原发性肝癌的易感基因型,rs2291778位点T等位基因是原发性肝癌的非易感等位基因.多位点多基因联合作用对于原发性肝癌的发生可能具有协同作用.
    목적 연구조공microRNA성숙적통로기인(DICERI、RAN급GEMIN4기인)표첨단핵감산다태성(tSNP)여원발성간암유전역감성적상관성.방법 채용1∶1배대병례-대조연구,장2008년9월지2010년12월재정주모량개교학의원취진적532례원발성간암환자납입병례조,장532명건강개체납입대조조,대기진행면대면조사병채집외주정맥혈5ml.종DICER1、RAN급GEMIN4기인중사선tSNP,채용PCR-RFLP혹등위기인특이PCR기술대연구대상진행기인분형,응용다인소조건logistic회귀급다인소강유법(MDR)분석tSNP여원발성간암역감성적관계급기여배경인소적교호작용.결과 재소사선적DICER1、RAN급GEMIN4기인tSNP중,rs14035위점CC、CT、TT기인형재병례조중적빈솔분별위67.29％ (358/532)、28.20％ (150/532) 、4.51％ (24/532),재대조조적빈솔분별위70.30％(374/532)、28.20％ (150/532)、1.50％( 8/532)(x2=8.35,P ＜0.05)；rs1045491위점GG、GA、AA기인형재병례조중적빈솔분별위71.05％ (378/532)、26.69％( 142/532)、2.26％(12/532),재대조조적빈솔분별위80.45％(428/532)、18.42％(98/532)、1.13％(6/532)(x2 =13.17,P＜0.01)；rs2291778위점GG、GT、TT기인형재병례조중적빈솔분별위53.38％( 284/532)、40.23％(214/532)、6.39％( 34/532),재대조조적빈솔분별위25.94％ (138/532)、63.91％(340/532)、10.15％( 54/532)(x2=83.71,P＜0.01).rs14035위점TT기인형(OR=2.54,95％CI:1.19 ～6.32)、rs1045491위점GA기인형(OR=1.74,95％CI:1.08 ～2.66)시원발성간암적역감기인형,rs2291778위점적GT기인형(OR =0.52,95％ CI:0.43～0.75)화TT기인형(OR=0.62,95％CI:0.46 ～0.86)시원발성간암적비역감기인형.단체형분석현시,단체형3 (AACTGGGT)(OR=1.42,95％CI:1.10～1.82)화단체형5(AGCCAGCC)( OR=1.36,95％ CI:1.02～1.80)가증가간암발병풍험,이단체형2( AACTATCC)(OR=0.69,95％CI:0.52 ～0.91)화단체형6(AACTGTGT)(OR =0.61,95％ CI:0.45～0.81)가강저원발성간암발병풍험.구유rs1045491(등위기인A)、rs14035(등위기인T)화HBV감염적교호조합적인군시원발성간암적고발인군(OR=3.72,95％ CI:2.38～ 5.56).결론 rs14035위점TT기인형、rs1045491위점GA기인형시원발성간암적역감기인형,rs2291778위점T등위기인시원발성간암적비역감등위기인.다위점다기인연합작용대우원발성간암적발생가능구유협동작용.
    Objective This study aimed to understand the correlation between tag single nucleotide polymorphisms (tSNP) of microRNA regulatory genes and the gentic susceptibility of primary liver cancer.Methods 1∶ 1 case-control study was applied in this research.A total of 532 primary liver cancer patients in 2 teaching hospitals in Zhengzhou city were enrolled as case group.532 healthy individuals were enrolled as control group.The subjects were surveyed by a face-to-face interview and 5 ml of peripheral venous blood were collected.Candidate tSNP were screened from DICER1,RAN and GEMIN4 gene,respectively.PCR-RFLP or Allele specific PCR was applied for genotyping of the subjects.Conditional logistic regression model and Multifactor-Dimensionatity Reduction method were applied for analyzing the correlation between tSNP of above genes and gentic susceptibility of primary liver cancer.The gene-environment interaction was also analyzed.Results The frequencies of genotype CC,CT,TT in rs14035 locus were 67.29％ ( 358/532 ),28.20％ ( 150/532 ),4.51％ ( 24/532 ) in case group,and 70.30％ ( 374/532 ),28.20％ ( 150/532),1.50％ ( 8/532 ) in control group,respectively( x2 =8.35,P ＜ 0.05 ).The frequencies of genotype GG,GA,AA in rs1045491 locus were 71.05％ (378/532),26.69％ (142/532),2.26％ ( 12/532) in case group,and 80.45％ (428/532),18.42％ (98/532),1.13％ (6/532) in control group,respectively( x2 =13.17,P ＜ 0.01 ) ;the frequencies of genetype GG,GT,TT in rs2291778 locus were 53.38％ (284/532),40.23％ (214/532),6.39％ (34/532) in case group,and were 25.94％ ( 138/532),63.91％ (340/532),10.15％ (54/532) in control group( x2 =83.71,P ＜0.01 ).TT genotype in rs14035locus ( OR =2.54,95％ CI:1.19 - 6.32 ) and GA genetype in rs1045491 locus ( OR =1.74,95％ CI:1.08- 2.66 ) were susceptible genotype of primary liver cancer,whereas GT (OR =0.52,95％ CI:0.43 -0.75 ) and TT genotype ( OR =0.62,95 ％ CI:0.46 - 0.86 ) in rs2291778 locus were protective genotype.Haplotype analysis showed that haplotype 3(AACTGGGT) ( OR =1.42,95％ CI:1.10 - 1.82) and haplotype 5( AGCCAGCC ) increased the risk of occurrence of primary liver cancer ( OR =1.36,95％ CI:1.02 -1.80),whereas haplotype 2 ( AACTATCC ) ( OR =0.69,95％ CI:0.52 - 0.91 ) and haplotype 6(AACTGTGT) (OR =0.61,95％ CI:0.45 -0.81 ) decreased the risk.Subjects exposed to allele A of rs1045491,allele T of rs14035 and HBV infection intend to be the high risk population of primary liver cancer (OR=3.72,95％CI:2.38 -5.56).Conclusion Genotypes of TT in rs14035 locus,and GA in rs1045491 locus may be susceptible genotypes of liver cancer carcinogenesis.T allele in rs2291778 locus is a non-susceptible allele of primary liver cancer.Combined effects of multigene alleles and multi-locus genotype may have a synergistic role in the carcinogenesis of liver cancer.
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