【作者】 宫立国； 邱广蓉； 姜辉； 徐小延； 朱宏玉； 孙开来；

【Author】 GONG Li-guo,QIU Guang-rong, JIANG Hui,XU Xiao-yan,ZHU Hong-yu,SUN Kailai.(Department of Medical Genet-ics,China Medical University,Shenyang, 110001 , P.R.China); (Department of Cardiac Surgery,Military District Hospi-tal,Shenyang,Liaoning,110006,P.R.China)

【机构】 中国医科大学遗传教研室； 沈阳军区总医院心脏外科；

【摘要】 目的在人类单纯性先天性心脏病(congenital heart disease,CHD)易感区域12q13内,选取HoxC4、HoxC5、HoxC6基因内4个已知单核苷酸多态(single nucleotide polymorphism,SNP)G7471T、C16476T、A17860G、A36130G,检测其在单纯性CHD患者和正常人群中的分布情况,分析各个SNP位点及所构成单倍型与单纯性CHD的相关性。方法应用限制性片段长度多态性(RFLP)和变性高效液相色谱法(DHPLC)结合测序,分析108名单纯性先天性心脏病患者及200名正常人4个SNP位点基因型;应用列联表法统计分析患者组和对照组各SNP位点基因型及等位基因频率;应用PHASE软件构建单倍型并统计分析患者组及对照组单倍型频率是否存在差异。结果C16476T未检测到多态;位于HoxC5基因3’侧翼序列的SNP位点A17860G等位基因频率及基因型频率在患者组和对照组中的分布差异显著,患者组G等位基因频率明显高于对照组(P<0.05);单倍型分析可见4种单倍型在患者组和对照组中的分布频率有统计学意义(P<0.005):G7471/G17860/G36130和G7471/G17860/A36130为人群中常见单倍型,与对照组相比,患者组中G7471/G17860/G36130、T7471/A17860/A36130两种单倍型频率较高。结论HoxC5基因3’侧翼序列的SNP位点A17860G与单纯性CHD有明显的相关性,具有G等位基因的人发生CHD的危险性相对增高;3个SNP位点所构成的单倍型有一定意义,可能与单纯性CHD易感基因相连锁。更多还原

【Abstract】 Objective In the candidate region 12ql3 of simple Congenital Heart Disease(CHD),we chose four single nucleotide poly-morphisms(SNP) in HoxC4 gene to investigate single SNP and haplotypes distribution in simple CHD patients and normal people. Methods We analyzed genotype of 4 SNPs in 108 simple CHD patients and 200 normal people by RFLP and DHPLC. Legally constituted authority statistical analysis was applied to analyze SNP genotype frequency and gene frequency in patients and control group; Then we established haplotypes and analyzed their frequency in two groups by PHASE software. Results C16476T polymorphism was not be detected; A17860G located in 3’ flanking sequence of HoxCS gene has significant difference between two groups, the G allele frequency in simple CHD patients was higher than those in healthy control(P<0. 05); Distributive frequencies of 4 haplotypes have marked difference (P<0.005). Conclusion A17860G which located in 3’ flanking sequence of HoxC5 gene is associated with simple CHD, the possibility getting CHD in the person with G17860 is more than those with A17860; The haplotype of 3 SNPs may be linkage with susceptible gene of simple CHD.更多还原