Analysis of NKX2-5 in 439 Chinese Patients with Sporadic Atrial Septal Defect.

BACKGROUND The NKX2 gene family is made up of core transcription factors that are involved in the morphogenesis of the vertebrate heart. NKx2-5 plays a pivotal role in mouse cardiogenesis, and mutations in NKx2-5 result in an abnormal structure and function of the heart, including atrial septal defect and cardiac electrophysiological abnormalities. MATERIAL AND METHODS To investigate the genetic variation of NKX2-5 in Chinese patients with sporadic atrial septal defect, we sequenced the full length of the NKX2-5 gene in the participants of the study. Four hundred thirty-nine patients and 567 healthy unrelated individuals were recruited. Genomic DNA was extracted from the peripheral blood leukocytes of the participants. DNA samples from the participants were amplified by multiplex PCR and sequenced on an Illumina HiSeq platform. Variations were detected by comparison with a standard reference genome and annotation with a variant effect predictor. RESULTS Thirty variations were detected in Chinese patients with sporadic atrial septal defect, and 6 single nucleotide polymorphisms (SNPs) had a frequency greater than 1%. Among the 30 variations, the SNPs rs2277923 and rs3729753 were extremely prominent, with a high frequency and odds ratio in patients. CONCLUSIONS Single nucleotide variations are the prominent genetic variations of NKX2-5 in Chinese patients with sporadic atrial septal defect. The SNPs rs2277923 and rs3729753 are prominent single nucleotide variations (SNVs) in Chinese patients with sporadic atrial septal defect.

Changes of regional cerebral oxygen saturation, S100β protein and neuron specific enolase and their relationship with perioperative neurocognitive disorders in patients undergoing total aortic arch replacement and trunk stenting / 西安交通大学学报(医学版)

【Objective】 To investigate the predictive value of regional cerebral oxygen saturation (rScO2) monitoring during total aortic arch replacement and stent trunk surgery for perioperative neurocognitive disorders (PND) and changes in plasma S100β protein and neuron-specific enolase (NSE) concentrations and their relationship with PND. 【Methods】 Sixty-five Stanford type A aortic dissection patients who planned to undergo total aortic arch replacement and trunk stenting were selected. Their rScO2 values were monitored throughout the operation and recorded after induction (T1), the beginning of CPB (T2), during deep hypothermic circulatory arrest (T3), rewarming to 36℃(T4), CPB stop for 1 hour (T5), and post-operation (T6). After induction (Ta), rewarming to 36℃ (Tb),1 h (Tc), 6 h (Td) and 24 h (Te) after cessation of cardiopulmonary bypass, central venous blood was collected from patients, and the concentrations of S100β protein and NSE in plasma were detected by ELISA. The patients were divided into PND group and non-PND group by the evaluation of MMSE scale at time of before operation, on the day of extubation, and 7 days after operation. 【Results】 The incidence of PND was 44.6%. The rScO2 value at T2 was significantly lower than that at T1 (P<0.05). The rScO2 value of PND group at T3 and T6 was significantly lower than that at T1 and non-PND group (P<0.05). The mean value of rScO2 and the minimum value of rScO2 in PND group were significantly lower than those in non-PND group, while rScO2 %max in PND group was significantly higher than that in non-PND group (P<0.05). The intraoperative critical value of rScO2 %max was >9.89%, the area under curve (AUC) was 0.658 (95% CI: 0.525-0.791, P<0.05), and sensitivity and specificity were 48.3% and 75.0%, respectively. The concentrations of S100β protein and NSE protein in PND group were significantly higher than those in non-PND group at Tc and Td (P<0.01). Compared with Ta, the concentration of S100β protein in PND group was significantly increased at Tc and Td (P<0.001), and the concentration of NSE protein was significantly increased at Tb-Te (P<0.01). CPB time was an independent risk factor for PND. 【Conclusion】 The occurrence of PND after total arch replacement and stenting may be related to the decrease of rScO2 and the increase of S100β protein and NSE protein. Intraoperative rScO2 %max >9.89% can be a potential predictor of PND.