Exploring Genetic Diversity of SOD2 and POU5F1 for Congenital Heart Disease in the Southwest Chinese Population.

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. χ² 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.