rs2857595

A case-control study of 273 DCM patients and 548 controls in the Chinese Han population examined seven genetic variants associated with cardiac neonatal lupus. The study found that the T allele of rs3134942 in NOTCH4 increased DCM risk by 61% (OR=1.61, 95% CI: 1.15-2.27, P=6.57×10⁻³) in additive and dominant models. Additionally, rs2472299 in CYP1A2 was associated with reduced DCM risk in the dominant model (OR=0.72, P=4.24×10⁻²) and correlated with smoking status in patients.

Pathway-based GWAS in 116 cardiac neonatal lupus children and 3,351 controls identified significant enrichment of genetic associations in genes related to fibrosis (P=2.27×10⁻⁹), apoptosis (P=7.67×10⁻⁷), and innate immunity (P=2.53×10⁻⁶). The strongest non-HLA associations were ST8SIA2 (rs1487982, OR=2.20), ITGA1 (rs2432143, OR=2.31), and CSMD1 (rs7002001, OR=2.41), implicating dysregulation of inflammatory and fibrotic pathways in cardiac manifestations of neonatal lupus.

Genome-wide association study of 116 children with cardiac neonatal lupus (116 cases, 3,351 controls) identified 17 significant SNPs in the HLA region at 6p21, with the strongest association at rs3099844 (OR 3.34, P=4.52×10⁻¹⁰) near the MICB gene. Non-HLA associations were found at rs743446 (21q22, OR 2.40, P=5.45×10⁻⁶), rs2403106 (12q21, OR 2.48, P=2.62×10⁻⁶), rs1391511 (10p15, OR 1.84, P=6.6×10⁻⁶), and rs1890645 (1q31, OR 2.98, P=3.52×10⁻⁶). Results suggest genetic polymorphisms in inflammatory and apoptotic pathways contribute to cardiac injury in fetuses exposed to maternal anti-Ro/SSA antibodies.