Supplementary Material for: A common variant in NID1 gene associated with the prognosis of heart failure

Introduction Previous study has demonstrated the protective effect of NID1 on myocardial infarction. This study aimed to assess the correlation between NID1 polymorphisms and the prognosis of heart failure (HF). In this study, we aimed to evaluate the association of NID1 polymorphisms with heart failure (HF). Methods A total of 1000 patients with HF were enrolled in the discovery cohort. Genotyping was conducted to assess the relationship between common variants in the NID1 gene and the prognosis of HF. A replication cohort involving 2266 HF patients was used to validate the association between variants and the prognosis of HF. A series of function analysis were conducted to illuminate the underlying mechanism. Results Synonymous variant rs3738530 was identified to be associated with the prognosis of HF in both the discovery cohort (adjusted P = 0.006, HR = 1.58, 95% CI= 1.14-2.19) and replication cohort (adjusted P = 0.005, HR = 1.83, 95% CI= 1.20-2.80). Western blot analysis demonstrated that the protein level of NID1 was significantly higher in the rs3738530-T allele compared to the A allele (P < 0.05). Transcription assays indicated that individuals with the rs3738530-AT+TT genotype exhibited elevated levels of NID1 mRNA relative to those with the AA genotype. Apoptosis assay indicated that overexpression of NID1 could protect AC16 cells from H/R-induced apoptosis. Furthermore, patients with rs3738530-AT+TT genotype exhibited a higher left ventricular ejection fraction and decreased left ventricular end-diastolic diameter compared to those with rs3738530-AA genotype (P< 0.05). Conclusion Common variant rs3738530 in the NID1 gene is associated with the prognosis of HF. NID1 may be a promising therapeutic target for HF in the future.