【摘要】 目的检测分析单核苷酸多态(SNP)位点在圆锥动脉干畸形患者和正常人群中的分布情况,以及与所构成单倍型与圆锥动脉干畸形的相关性。方法应用聚合酶链反应-限制性片段长度多态性方法分析130例圆锥动脉干畸形患者及200名正常人3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G2963A位点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(χ2=8·14,P<0·005);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差异有统计学意义(χ2=22·39P<0·005):G2857/G2963/A6571和G2857/G2963/T6571为人群中常见单倍型。患者组中G2857/G2963/A6571、C2857/A2963/T6571两种单倍型频率较对照组高。结论TBX1基因编码区的SNP位点G2963A与圆锥动脉干畸形有明显的相关性,具有G等位基因的人发生圆锥动脉干畸形的危险性相对增高;3个SNP位点所构成的单倍型有一定意义,可能与圆锥动脉干畸形易感基因相连锁。更多还原

【Abstract】 Objective To investigate the distribution of the single nucleotide polymorphism (SNP) sites in TBX1 gene and the distribution of related haplotypes in the patients with contruncal defects (CTD) and normal people. Methods The genotypes of the 3 selected SNPs: G2857C(rs737868), G2963A(rs28649236), and A6571T(rs28939675) in TBX1 gene were analyzed by PCR-RFLP among 130 patients with CTD and 200 normal people. Contingency table was applied to analyze the frequencies of these SNP genotypes and related alleles. PHASE software was used to construct the haplotypes and analyze the haplotype frequencies in these 2 groups. Results There were no significant differences in the allele frequency and genotype rates of the SNPs G2587C and A6571T between the CTD patients and normal controls (all P>0.05). However, the allele frequency and genotype rates of the SNP G2963A were significant different between he CTD patients and normal controls: the G allele frequency in the CTD patients was 53.8%, significantly higher than that in the normal controls (42.5%, χ~2=8.14, P<0.005); and the AA genotype rate of the CTD patients was 21.6%, significantly lower than that of the controls (38.0%), and the GA genotype rate in the CTD patients was 49.2%, significantly higher than that in the controls (39.0%) (both χ~2=9.9, P<0.05). The haplotype frequencies of G2587/ G2963/ A6571 and G2587/A2963/T6571 of the CTD patients were 49.2% and 14.6% respectively, both significantly higher than those of the normal controls (36.3% and 9.5% respectively), and the haplotype frequencies of G2587/ G2963/ T6571 and G2587/A2963/A6571 in the CTD patients were 34.6% and 3% respectively, both significantly lower than those in the normal controls (48.3% and 18% respectively) (χ~2=22.39, P<0.005).Conclusion The SNP site G2963A located in the coding-region of TBX1 gene is associated with CTD. The persons with G2963 have higher risk of CTD than those with A2963. The haplotypes constructed with these 3 SNP sites may be linked with the susceptibility gene of CTD.更多还原