NPAS4 Polymorphisms Contribute to Coronary Heart Disease (CHD) Risk.

As genetic inheritance is an inevitable risk factor in the development of coronary heart disease (CHD), it is critical to identify the polymorphisms of CHD risk. This study explored whether the NPAS4 polymorphisms are related to the CHD risk in the Chinese Han population. Five SNPs in NPAS4 were genotyped using Agena Mass ARRAY from 499 CHD and 500 controls. RT-PCR detected the NPAS4 expression levels in peripheral blood mononuclear cells from 50 CHD and 50 controls. χ test compared the distributions of gender, allele and genotypes frequencies between cases and controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). MDR analyzed the SNP-SNP interactions on risk of CHD. U test compared the differences in gene expression between different groups. The results showed that rs4466842 was correlated with an increased CHD risk in overall, males and age ≤ 60; rs117186164 and rs12785321 were significantly related to an increased CHD risk in male and age ≤ 60, respectively; haplotype AC was significantly correlated with an increased CHD risk. SNP-SNP interactions results showed that the best model was the four-locus model was the combination of rs117770654, rs117957381, rs12785321, and rs4466842 (CVC = 10/10, Testing Sensitivity = 0.647). The expression levels of NPAS4 in the case group (0.365 ± 0.139) were significantly lower than that in the control group (0.782 ± 0.224) (P < 0.001). The results revealed that SNPs in NPAS4 may play an important role in the occurrence and development of CHD.