The Study Of ISL1Gene Polymorphism Associated With Congenital Heart Disease

Objective:We conducted a case-control study to examine SNPs (rs41268421. rs1017) to identify whether a common variant in ISL1influences susceptibility to sporadic CHD in our Chinese population. In this study, we would like to provide experimental information on prevention and reduction the motility of CHD, and establishment the cure measure.Methods:1. Searching all SNPs in ISL1gene, by using NBCI website SNPs database, meanwhile referring to the relevant literature, finally settled the SNPs in ISL1gene we planned to study.2. A case-control study was performed. The case group included35children who were diagnosed as CHD between December2011and December2012in the Tianjin Children’s Hospital. Boys18cases, girls17cases, male to female ratio was1.06:1, age7months to3years, mean age23±6months. All the cases had CHD diagnosed by ultrasound and confirmed in surgical operations. Of the35CHD cases,18had VSD (ventricular septal defect),17had ASD (atrial septal defect).30age-and gender-matched children who came from clinical department waiting for operation were enrolled as the control group. Boys15cases, girls15cases, male to female ratio of1:1, age6months to3years, mean age22±9months. All the study subjects are Chinese Han children. We have collected2ml blood from each CHD patients and controls, anticoagulated by sodium citrate, and preserved in the condition of80℃.3. Genomic DNA was prepared from peripheral venous blood (2ml) using a genomic DNA isolation reagent kit. Polymerase chain reaction (PCR) and gene sequence analysis were applied to detect the single nucleotide polymorphism of ISL1gene rs41268421and rs1017. The differences about allele and genotype frequencies in different groups were compared, and the haplotype was analyzed.Results:1. Three genotypes (GG, GT and TT) were detected at ISL1gene SNP 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, P<0.05).2. Three genotypes (AA, AT and TT) were detected at SNP 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).3. The haplotype was analyzed in the two SNPs(rs41268421%rs1017), and Four kinds of haplotype were detected in the two SNPs sites and TT type increased the risk of CHD (OR=7.813).Conclusions:1. Polymorphisms of ISL1gene SNP rs41268421and rs1017may be associated with CHD susceptibility in Chinese Han children.2. T allele of ISL1gene SNP rs41268421is a risk factor of CHD in Chinese Han children.3. T allele of ISL1gene SNP rs1017is thought to increase risk of CHD in Chinese Han children.4. The haplotype was analyzed in the two SNPs(rs41268421、rs1017),and the Haplotype TT has a higher risk of CHD in Chinese Han children.