HOLE基因外显子2区SNP与先天性心脏病的关联研究

Correlation between SNPs of HOLE gene and congenital heart disease

目的:研究HOLE基因外显子2区SNP与人类先天性心脏病(CHD)的相关性。方法:以病例组179例CHD患者和对照组183例门诊体检健康人为研究对象,酚-氯仿法提取外周血DNA,PCR扩增产物经变性丙烯酰胺电泳鉴定基因型,应用卡方检验分析组间基因型频率及等位基因频率差异。结果:(1)粤黔两地汉族人群中存在HOLE基因SNPrs10569304的插入缺失(GCC/-)多态性,对应为等位基因A/B。(2)对照组和病例组的基因型频率及等位基因频率符合Hardy-Weinberg平衡,两组AA、AB和BB三种基因型频率分别为21.31%、54.09%、24.59%和16.75%、46.36%、36.87%,经卡方检验基因型分布差异有统计学意义(χ2=6.51,P<0.05),与对照组相比,病例组中BB基因型频率升高,AA、AB基因型频率降低。(3)对照组与病例组A和B等位基因频率分别为48.36%,51.64%和39.94%,60.06%,病例组B等位基因频率显著高于对照组,分布差异有显著性(χ2=5.20,P<0.05)。结论:粤黔两地汉族人群中HOLE基因SNPrs10569304存在插入缺失(GCC/-)多态性,具有BB基因型的个体罹患CHD的危险度增高。

Objective To investigate the correlation between SNP of HOLE gene exon district 2 and congenital heart disease （CHD）. Methods 179 patients with CHD （CHD group） and 183 healthy people （control group） were included in the study. DNA was abstracted from the peripheral blood by phenol-chloroform method and proliferated by PCR, and the genotypes of which were identified by PAGE. The genotypic frequencies and allele frequencies were analyzed by ehi-square test. Results There were insertion-deletion （GCC/-） polymorphism of SNP （rs10569304） which are defined as allele A and B of the HOLE gene in Southern Chinese people. The genotypie frequencies and allele frequencies in both groups met the Hardy- Weinberg equilibrium. The genotypic frequencies of AA, AB, and BB were 21.31%, 54.09%, 24.59% and 16.75%, 46.36%, 36.87% in control group and in CHD group. There were significant differences of the distribution of the three genotypes frequencies between the two groups （X^2 = 6.51, P 〈 0.05）. Comparing with the control group, the frequency of BB in CHD group was higher but the AA and AB was lower. The allele frequencies of A and B were 48.36% and 51.64% in control group, 39.94% and 60.06% in CHD group. The frequency of allele B in CHD group was higher than that in control group （X^2 = 5.20,P 〈 0.05）. Conclusion There are insertion-deletion （GCC/-） polymorphism of SNP （rs10569304） in the Southern Chinese people, and there is higher risk of CHD for people whose HOLE gene involving BB genotype.