RESUMO
The aim of the present study was to investigate whether methylation of the angiotensin I converting enzyme 2 (ACE2) promoter increases the risk of essential hypertension (EH). A total of 96 patients with EH were recruited and 96 sex and agematched healthy controls. Methylation of 5 CpG dinucleotides in the ACE2 promoter was quantified using bisulfite pyrosequencing. Logistic regression and multiple linear regression were used to adjust for confounding factors and the generalized multifactor dimensionality reduction (GMDR) method was applied to investigate highorder interactions. Methylation of CpG4 (adjusted P=0.020) and CpG5 (adjusted P=0.036) was significantly higher in patients with EH, with frequency 97.56±5.65% and 12.75±4.15% in EH individuals and 95.73±9.11% and 11.47±3.67% in healthy controls. GMDR detected significant interaction among the 5 CpG sites (odds ratio=7.33, adjusted P=0.01). Furthermore, receiver operating characteristic curves identified that CpG5 methylation was a significant predictor of EH. Notably, CpG2 methylation was significantly higher in males than in females (adjusted P=0.018). Conversely, CpG5 methylation was significantly lower in males (adjusted P=0.032). These results indicated that aberrant methylation of the ACE2 promoter may be associated with EH risk. In addition, sex may significantly influence ACE2 methylation.
Assuntos
Metilação de DNA , Hipertensão Essencial/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Regiões Promotoras Genéticas , Enzima de Conversão de Angiotensina 2 , Biomarcadores , Estudos de Casos e Controles , Ilhas de CpG , Hipertensão Essencial/metabolismo , Feminino , Loci Gênicos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
Recently, the detection of occult cancer cells in peripheral blood has received a great deal of attention regarding the prediction of postoperative cancer recurrence and for novel strategies of adjuvant therapy. The aim of this study was to establish a new molecular diagnostic method of detecting circulating tumor cells. Gastric cancer SGC-7901 cells in 2 ml blood from healthy volunteers were serially diluted. Additional peripheral blood samples were collected from 90 patients and 27 healthy volunteers. Real-time reverse transcription-polymerase chain reaction was used to detect the levels of microRNA-106a (miR-106a) and microRNA-17 (miR-17). Receiver operating characteristics (ROC) curves were constructed. In recovery experiments, a significant correlation between the number of cancer cells and the levels of both miR-106a (r = -0.906, p = 0.037) and miR-17 (r = -0.912, p = 0.031) was found. In preoperative and postoperative patient groups, miR-106a and miR-17 levels were significantly higher than those in controls. The areas under the ROC curve for miR-106a, miR-17, and combination were 0.684 (p = 0.0066), 0.743 (p = 0.0001), and 0.741 (p = 0.0002), respectively. Our results indicate that the detection of miRNA in peripheral blood may be a novel tool for monitoring circulating tumor cells in patients with gastric cancers.