MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. METHODS: We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. RESULTS: When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. CONCLUSIONS: Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. KEY WORDS: Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

The role of aquaporin 1 activated by cGMP in myocardial edema caused by cardiopulmonary bypass in sheep.

BACKGROUND/AIMS: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. METHODS: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. RESULTS: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h) compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition of cGMP pathway also can significantly decrease the degree of myocardial edema (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function in sheep after CPB. Results of in vitro experiments showed the same changing trends as in vivo. CONCLUSION: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.