Associations between ABCC2 gene 1249G>A polymorphism and congenital isolated septal defects

Abstract

Objective To explore the associations between ABCC 2 gene 1249G>A polymorphism and congenital isolated septal defects. Methods From March 2013 and March 2015, a total of 300 children with congenital isolated septal defects from Department of Pediatric Cardiovascular, West China Second University Hospital, Sichuan University were selected as research subjects and enrolled as case group, while 300 children with respiratory tract infections and age, gender matched during the same period in the same hospital were recruited as control group. Case group was further divided into the perimembranous ventricular septal defect (Pm-VSD) subgroup (n=150) and the secondary atrial septal defect (s-ASD) subgroup (n=150). Genotypings of the ABCC 2 gene 1249G>A polymorphism in case group and control group were performed by PCR sequencing. Independent-samples t test was used to compared the ages between case group and control group, Pm-VSD subgroup and control group, s-ASD subgroup and control group, respectively. Chi-square test was used to compare the gender ratios, and GG, GA, AA genotypes of ABCC 2 gene 1249G>A polymorphism between case group and control group, Pm-VSD subgroup and control group, s-ASD subgroup and control group, respectively. Single-factor unconditional logistic regression analysis was used to compare genotypes frequencies of different genetic models in ABCC 2 gene 1249G>A polymorphism between case group and control group, Pm-VSD subgroup and control group, s-ASD subgroup and control group, respectively. This study was approved by the Ethics Committee of Human Beings in West China Second University Hospital, Sichuan University and the guardians of every subject signed informed consent of clinical research. Results ①There were no significant differences in the gender ratio and age between case group and control group, Pm-VSD subgroup and control group, s-ASD subgroup and control group, respectively (P>0.05). ②The genotypes distributions of ABCC 2 gene 1249G>A polymorphism of case group, Pm-VSD subgroup, s-ASD subgroup, and control group all were in line with Hardy-Weinberg equilibrium law (χ2=0.880, P=0.820; χ2=0.246, P=0.913; χ2=1.042, P=0.748; χ2=0.110, P=0.925). ③The GG, GA, AA genotypes frequencies of ABCC 2 gene 1249G>A polymorphism in case group were 67.0% (201/300), 30.7% (92/300), and 2.3% (7/300), respectively, 80.7% (242/300), 18.0% (54/300), and 1.3% (4/300), respectively in control group, 62.3% (94/150), 35.1% (52/150), and 2.6% (4/150), respectively in Pm-VSD subgroup, 71.3% (107/150), 26.7% (40/150), and 2.0% (3/150), respectively in s-ASD subgroup. The genotypes distributions of ABCC 2 gene 1249G>A polymorphism were significantly different between control group and case group, Pm-VSD subgroup, and s-ASD subgroup (χ2=14.503, P=0.001; χ2=17.132, P A polymorphism showed that, there were statistically significant differences between case group and control group in genotypes frequencies of recessive model (GG, GA/AA) (OR=2.0, 95%CI: 1.4-3.0, P 0.05). ⑤The stratified analysis of congenital heart disease (CHD) subtypes demonstrated that, there were statistically significant differences between Pm-VSD subgroup and control group in genotypes frequencies of recessive model (GG, GA/AA) (OR=2.5, 95%CI: 1.6-3.9, P<0.001) and allele frequencies of G and A (OR=2.2, 95%CI: 1.5-3.2, P<0.001), which meant that in the recessive model (GG, GA/AA), the onset risk of Pm-VSD in children with GA/AA genotypes was 2.5 times of that in children with GG genotype; and the onset risk of Pm-VSD in children with A allele is 2.2 times of that in children with G allele. And there were statistically significant differences between s-ASD subgroup and control group in genotypes frequencies of recessive model (GG, GA/AA) (OR=1.6, 95%CI: 1.0-2.6, P=0.040) and allele frequencies of G and A (OR=1.6, 95%CI: 1.0-2.4, P=0.038), which meant that in the recessive model (GG, GA/AA), the onset risk of s-ASD in children with GA/AA genotypes was 1.6 times of that in children with GG genotype; and the onset risk of s-ASD in children with A allele is 1.6 times of that in children with G allele. Conclusion There is a significant association between ABCC 2 gene 1249G>A polymorphism and congenital isolated septal defects. Key words: ABCC 2 gene; 1249G>A polymorphism; Heart septal defects, ventricular; Heart septal defects, atrial; Heart disease, congenital; Fetus