Association of NF-κB1 gene polymorphisms with coronary artery disease in a Han Chinese population.

Nuclear factor (NF)-κB is a transcription factor that controls cell proliferation, differentiation, and immunity. Activated NF-κB1 is associated with the pathogenesis of coronary artery disease (CAD) and genetic polymorphisms in NF-κB1 have a plausible role in modulating the risk of CAD. To identify markers that contribute to the genetic susceptibility to CAD, we examined the potential association between CAD and single nucleotide polymorphisms (SNPs; rs28362491, rs230531, rs230528, rs1005819, rs4648055, rs3774964, and rs3774968) in the NF-κB1 gene using SNaPshot SNP genotyping assay. Participants included 361 patients with CAD and 385 healthy controls. The genotype and allele frequencies of the rs28362491 (promoter region) polymorphism in the CAD patients were significantly different from those in the healthy controls. The frequency of the D allele was significantly higher in CAD patients than in the healthy controls (P = 0.005 after Bonferroni correction). Strong linkage disequilibrium was observed in one block (D' > 0.9). Haplotype analysis revealed that haplotypes in block 1 of the NF-κB1 gene did not display a risk or protective effect (P > 0.05). These data suggest that NF-κB1 gene polymorphisms confer susceptibility to CAD and also support the notion that dysfunction of NF-κB1 is involved in the pathophysiological process of CAD.

Association between interleukin-17A polymorphism and coronary artery disease susceptibility in the Chinese Han population.

Coronary artery disease (CAD) is a major global health problem. In China, the incidence of CAD and the rate of mortality arising from it have increased every year. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by activated T cells, and it may be involved in the development of CAD. Genetic polymorphisms in functional regions of the IL17A gene have a plausible role in modulating the risk of CAD. To evaluate the role of IL17A polymorphisms as a risk factor for CAD, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory regions of IL17A. This study examined the potential association between CAD and five SNPs (rs8193037, rs8193036, rs3819024, rs2275913, and rs3748067) of the IL17A gene. The allelic or genotypic frequencies of the rs8193037 (promoter region) and rs8193036 (promoter region) polymorphisms in CAD were significantly different from those in healthy controls. The CAD subjects had a significantly lower frequency of the A allele of rs8193037 (P = 0.009, OR = 1.772, 95%CI = 1.146- 2.742) and the T allele of rs8193036 (P = 0.010, OR = 1.754, 95%CI = 1.139-2.701). Strong linkage disequilibrium was observed in one block (D' > 0.9). Significantly fewer T-G-G-A haplotypes (P = 0.045) were found in CAD subjects in block 1. These data suggest that IL17A gene polymorphisms confer susceptibility to CAD, and support the notion that dysfunction of IL-17A is involved in the pathophysiological process of CAD.

Protective role of neuregulin-1 toward doxorubicin-induced myocardial toxicity.

The aim of this study was to investigate the role of the rat neuregulin-1 (NRG-1) protein in reducing doxorubicin (DOX)-induced myocardial toxicity and its underlying mechanism. The prokaryotic expression of the NRG-1 protein and the CCK8-determined activity of rat primary myocardial cells were evaluated under different DOX concentrations. Myocardial cells were divided into three groups: the control group, the 5 µM DOX (DOX5) group, and the DOX5+NRG-1 group. Western blotting was used to determine the Na+-Ca2+ exchanger (NCX-1) and cardiac myosin light-chain kinase (cMLCK) protein expression levels and real-time quantitative polymerase chain reaction methods were used to determine the mRNA expression levels. The prokaryotic expression of NRG-1 in the DOX5 group produced toxicity in the rat myocardial cells, and cell activity was significantly restored with the addition of NRG-1. The protective effect of NRG-1 was limited at higher DOX concentrations (DOX10), and the degree of cellular activity restoration was positively correlated with NRG-1 concentration. The addition of NRG-1 to DOX5 intervention inhibited NCX-1 protein and mRNA expression, and increased cMLCK protein and mRNA expression. In conclusion, DOX-induced toxicity in rat myocardial cells could be protected by NRG-1, and the mechanism may be related to the role of NRG-1 in up-regulating the cMLCK expression level and down-regulating the NCX-1 expression level.