Yunnan Fuwai Cardiovascular Hospital.
Department of Medical Genetics, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College.
Int Heart J. 2024;65(4):723-729. doi: 10.1536/ihj.24-068.
Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies, with atrial septal defect (ASD) and ventricular septal defect (VSD) being the most common forms of simple CHD, which involve a large number of susceptibility genes. However, despite extensive research, the etiology of ASD and VSD remains unclear. Yunnan Province has advantages in exploring CHD pathogenesis due to its unique genetic background. Therefore, we aimed to evaluate the association between single nucleotide polymorphisms (SNPs) of genes and susceptibility to simple CHD in a specific population by means of a case-control study. A total of 337 healthy controls and 767 patients with simple CHD (501 ASD and 266 VSD) from China were recruited. Candidate SNPs were identified through whole-genome sequencing of pooled CHD patients and controls (pool-seq). Genotyping from 1,104 samples was performed, and stratified analysis was conducted to explore the association between positive SNPs and CHD subtypes. χ tests and logistic regression were used to analyze the relationship between each SNP and simple CHD. Of 11 SNPs identified, SOD2 rs62437333 (P = 0.005) and POU5F1 rs3130504 (P = 0.017) showed differences between the control and ASD cohorts. In the dominant inheritance model hypothesis, rs62437333 allele C carriers had increased ASD (odds ratio (OR) = 2.04, P = 0.005) and combined simple CHD risk (OR = 2.33, P = 0.012) compared to DD genotype, while rs3130504 allele C carriers had increased ASD risk (OR = 1.121, P = 0.045) compared to DD genotype.
先天性心脏病（CHD）占所有重大先天性畸形的近三分之一，房间隔缺损（ASD）和室间隔缺损（VSD）是最常见的简单 CHD 形式，涉及大量易感性基因。然而，尽管进行了广泛的研究，ASD 和 VSD 的病因仍然不清楚。云南省由于其独特的遗传背景，在探索 CHD 发病机制方面具有优势。因此，我们旨在通过病例对照研究评估特定人群中基因单核苷酸多态性（SNP）与简单 CHD 易感性之间的关系。共招募了 337 名健康对照者和 767 名患有简单 CHD（501 例 ASD 和 266 例 VSD）的患者，这些患者来自中国。通过对 CHD 患者和对照者的基因组进行全基因组测序（pool-seq）来鉴定候选 SNP。对 1104 个样本进行基因分型，并进行分层分析以探讨阳性 SNP 与 CHD 亚型之间的关系。 χ检验和 logistic 回归用于分析每个 SNP 与简单 CHD 的关系。在确定的 11 个 SNP 中，SOD2 rs62437333（P = 0.005）和 POU5F1 rs3130504（P = 0.017）在对照组和 ASD 队列之间存在差异。在显性遗传模型假设下，与 DD 基因型相比，rs62437333 等位基因 C 携带者 ASD（优势比（OR）= 2.04，P = 0.005）和合并简单 CHD 风险（OR = 2.33，P = 0.012）均增加，而 rs3130504 等位基因 C 携带者 ASD 风险增加（OR = 1.121，P = 0.045）与 DD 基因型相比。
