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目的在人类单纯性先天性心脏病(congenital heart disease ,CHD)易感区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CDH的相关性。方法应用限制性片段长度多态性和变性高效液相色谱法结合测序,分析108例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有统计学意义,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中的分布频率有统计学意义(P<0·01) ;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、G7471/G17860/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。
Objective To select four known single nucleotide polymorphisms (SNPs) G7471T and C16476T in HOXC4, HOXC5 and HOXC6 genes in 12q13 susceptible region of human congenital heart disease (CHD) , A17860G, A36130G were detected in patients with simple CHD and normal distribution of the population, analysis of SNP loci and haplotypes and simple CDH correlation. Methods Using restriction fragment length polymorphism (PCR-RFLP) and denaturing high performance liquid chromatography combined with sequencing, the genotypes of four SNPs in 108 patients with simple congenital heart disease and 200 normal subjects were analyzed. The genotype and allele frequencies of each SNP locus in the control group and the control group were constructed. The haplotypes were constructed by PHASE software and the haplotype frequencies of patients and controls were statistically analyzed. Results No polymorphism was detected in C16476T. The distribution of A17860G allele and genotype at the SNP site of 3 ’flanking sequence of HOXC5 gene was significantly different between patients and controls. The G allele frequency (P <0.05). The haplotype analysis showed that the distribution frequencies of four haplotypes in patients and controls were statistically significant (P <0.01); G7471 / G17860 / G36130 and G7471 / G17860 / A36130 is a common haplotype in the human population. Compared with the control group, G7471 / G17860 / G36130 and G7471 / G17860 / A36130 have higher haplotype frequency. Conclusions The SNP A17860G of 3 ’flanking sequence of HOXC5 gene has obvious correlation with simple CHD. The risk of CHD in G allele of HOXC5 gene is relatively high. There are certain haplotypes Meaning, may be linked to simple CHD susceptibility genes.