胰岛因子1基因2个SNP位点与儿童先天性心脏病的相关性研究

目的：探讨天津地区汉族儿童胰岛因子1（Islet1，ISL1）基因2个单核苷酸多态性（SNP）位点rs41268421、rs1017与先天性心脏病（CHD）的相关性。方法：应用聚合酶链反应（PCR）和基因测序技术对35例CHD患儿和30名除外CHD儿童的rs41268421、rs1017位点进行检测，分别比较两个SNP位点基因型频率和等位基因频率在两组的分布情况，并进行单体型分析。结果：SNP位点rs41268421存在GG、GT、TT 3种基因型，CHD组T等位基因频率及携带T等位基因的基因型（包括GT和TT）频率高于对照组（P<0.05），携带T等位基因的儿童患CHD的危险是G等位基因的4.833倍；rs1017 位点存在AA、AT、TT 3种基因型，CHD组T等位基因频率及携带T等位基因的基因型（包括AT和TT）频率高于对照组（P<0.05），携带T等位基因的儿童患CHD的危险是A等位基因的4.491倍；2个SNPs位点得出4种单体型，以TT型儿童发生CHD的危险性最高（OR=7.813）。结论：天津地区汉族儿童中ISL1基因单体型TT的出现很可能会增加CHD的患病风险。

Association between two SNPs of ISL1 gene and congenital heart disease in children

OBJECTIVE: To investigate the association between 2 SNPs of ISL1 gene and congenital heart disease (CHD) in Tianjin Han children. METHODS: Polymerase chain reaction and DNA sequencing were used to detect 2 SNPs at rs41268421 and rs1017 sites of ISL1 gene, including 35 CHD cases and 30 non-CHD controls. Differences of genotype and allele frequencies of rs41268421 and rs1017 sites were compared, and haplotype analysis of the two sites was performed. RESULTS: Three genotypes (GG, GT and TT) were detected at ISL1 gene SNP rs41268421, and three genotypes (AA, AT and TT) were detected at SNP rs1017. At rs41268421, GT+TT genotypes and T allele frequencies in the CHD group were statistically higher than in the controls. The risk of CHD in children with T allele was significantly increased compared with children with G allele (OR=4.833). At rs1017, AT+TT genotypes and T allele frequencies in the CHD group were statistically higher than controls. The risk of CHD in children with T allele was greater compared with children with A allele (OR=4.491; P<0.05). Four kinds of haplotype were detected in the two SNPs sites and TT type increased the risk of CHD (OR=7.813). CONCLUSIONS: Haplotype TT may increase the risk of CHD in Tianjin Han children.