The Karachi Institute of Biotechnology and Genetic Engineering, University of Karachi, Karachi, Pakistan.
National Institute of Cardiovascular Diseases Pakistan Rafiqui (H.J.), Shaheed Road, Karachi, Pakistan.
BMC Cardiovasc Disord. 2024 Sep 27;24(1):516. doi: 10.1186/s12872-024-04035-2.
Congenital heart disease (CHD) is a lifelong abnormality present from birth. Multiple studies have shown that mutations in genes involved in heart development could cause congenital heart disease. The CITED2 gene works as a transcription factor in the hypoxic pathway for the development of the heart. Therefore, five CHD types, ventricular septal defect, atrial septal defect, atrioventricular septal defect, tetralogy of fallot, and patent ductus arteriosus, were evaluated by conducting a targeted single nucleotide polymorphism (SNP) analysis of the CITED2 gene variant rs375393125 (T > C). This study aimed to identify the association of CITED2 gene mutations in CHD patients.
Three hundred fifty samples, 250 from patients and 100 from controls, were collected for this genetic analysis. Allele-specific PCR and gel electrophoresis were used to identify the target missense mutations. The genotypic results of the CHDs were further validated through Sanger sequencing.
The frequency of the homozygous mutant (CC) in CHD patients was 48.4%, and of the heterozygous mutant (TC) genotype was 11.4%; these percentages are higher than controls (1%). The control samples had only one heterozygous TC and no homozygous CC genotype. The chi-square value was obtained at 103.9 with a probability of 0.05, more significant than the significance value of 21.03. The odds ratio was 43.7, which is > 1. The calculated value of ANOVA was 11.6, which was more significant than the F critical value of 3.7. As a result of sequencing, the mutant sample of each selected CHD type was found heterozygous or homozygous, and the results were like those obtained through conventional PCR.
The samples of CHD patients showed mutations. Therefore, the CITED2 gene SNP might be associated with CHD.
先天性心脏病（CHD）是一种从出生起就存在的终身异常。多项研究表明，参与心脏发育的基因突变可能导致先天性心脏病。CITED2 基因在心脏发育的低氧途径中作为转录因子发挥作用。因此，通过对 CITED2 基因变体 rs375393125（T>C）进行靶向单核苷酸多态性（SNP）分析，评估了 5 种 CHD 类型，即室间隔缺损、房间隔缺损、房室间隔缺损、法洛四联症和动脉导管未闭。本研究旨在确定 CITED2 基因突变与 CHD 患者的关联。
收集了 350 个样本，其中 250 个来自患者，100 个来自对照，进行了这项遗传分析。等位基因特异性 PCR 和凝胶电泳用于鉴定目标错义突变。通过 Sanger 测序进一步验证 CHD 的基因型结果。
CHD 患者的纯合突变（CC）频率为 48.4%，杂合突变（TC）基因型频率为 11.4%；这些百分比高于对照（1%）。对照样本仅有一种杂合 TC 且无纯合 CC 基因型。卡方值为 103.9，概率为 0.05，比 21.03 的显著性值更显著。优势比为 43.7，大于 1。方差分析的计算值为 11.6，比 3.7 的 F 临界值更显著。通过测序，发现每个选定的 CHD 类型的突变样本均为杂合或纯合，结果与常规 PCR 获得的结果相似。
CHD 患者的样本显示存在突变。因此，CITED2 基因 SNP 可能与 CHD 相关。
