NOTCH4 is a possible novel susceptibility gene for dilated cardiomyopathy in the Chinese population: A case-control study.

BACKGROUND: The incidence of dilated cardiomyopathy (DCM) has increased in recent years, and many studies have sought to further improve the general understanding of this condition. Previous studies have demonstrated that some single nucleotide polymorphisms (SNPs) associated with systemic lupus erythematosus also affect susceptibility to DCM, suggesting that immune-related diseases may share similar genetic susceptibility. Recent large-scale and genome-wide association studies have identified NCR3, NOTCH4, CYP1A2, ITGA1, OPRM1, ST8SIA2, and LINC00704 as genetic risk factors associated with cardiac manifestations of neonatal lupus. Here, we aimed to determine whether these SNPs conferred susceptibility to DCM in the Chinese Han population.

METHODS: We investigated the relationship between these polymorphisms and DCM risk in 273 patients with DCM and 548 healthy controls. Genotyping was performed using MassArray iPLEX system.

RESULTS: Logistic regression analysis indicated that the T allele of rs3134942 in NOTCH4 gene increased the risk of DCM by 61% compared with the G allele (Pa  = 6.57 × 10-3 ). The SNP rs3134942 was also significantly associated with increased DCM risk in the additive (Pa  = 6.57 × 10-3 ) and dominant models (Pa  = 1.01 × 10-2 ). Additionally, rs2472299 in CYP1A2 gene showed suggestive association with reduced risk of DCM in the dominant model (Pa  = 4.24 × 10-2 ) and was correlated with smoking status in patients with DCM (Pa  = 1.56 × 10-2 ).

CONCLUSIONS: Our findings suggested that rs3134942 in NOTCH4 may be involved in DCM risk. Further, studies in larger and ethnically diverse populations are required to confirm the results reported in this study.