Association between circulating levels of ACE2-Ang-(1–7)-MAS axis and ACE2 gene polymorphisms in hypertensive patients

Abstract

The angiotensin-converting enzyme 2-angiotensin-(1–7)-MAS axis (ACE2-Ang-[1–7]-MAS axis) plays an important role in the control of blood pressure. Some previous studies indicated that the genetic variants of ACE2 may have a potential to influence this axis. Therefore, the present study aimed at examining the association of ACE2 polymorphisms with circulating ACE2 and Ang-(1–7) levels in patients with essential hypertension.Hypertensive patients who met the inclusion criteria were enrolled in the present study. Three Tag single-nucleotide polymorphisms (rs2106809, rs4646155, and rs879922) in ACE2 gene were genotyped for all participants. Circulating ACE2 and Ang-(1–7) levels were detected by enzyme-linked immunosorbent assay.There were 96 (53.0%) females and 85 (47.0%) males participating in the present study. The circulating Ang-(1–7) levels were significantly greater in female patients carrying the rs2106809 CC or CT genotype compared with those carrying the TT genotype (1321.9 ± 837.4 or 1077.5 ± 804.4 pg/mL vs 751.9 ± 612.4 pg/mL, respectively; P = 0.029, analysis of variance), whereas the circulating Ang-(1–7) levels were comparable among genotypes in male patients. In addition, there was no significant difference in the circulating ACE2 levels among rs2106809 CC, CT, and TT genotype groups in both female and male patients. The circulating ACE2 and Ang-(1–7) levels were related to neither rs4646155 nor rs879922 in female or male patients.In conclusion, the rs2106809 polymorphism of the ACE2 gene may be a determinant of the circulating Ang-(1–7) level in female patients with hypertension, suggesting a genetic association between circulating Ang-(1–7) levels and ACE2 gene polymorphisms in patients with hypertension.

ACE2 polymorphisms associated with cardiovascular risk in Uygurs with type 2 diabetes mellitus

“…Although the roles of ACE2 gene polymorphisms (mutations or variants) on diabetes and other associated cardiovascular complications were incompletely understood, it may be related to the cross-talk between ACE2/Ang-(1–7)/Mas axis and ACE/Ang II/AT1 axis [ 48 ]. ACE2 gene polymorphisms (e.g., rs2106809 [ 49 ], rs2074192 [ 48 ]) were associated with downregulation of circulating Ang-(1–7). The deletion of ACE2 in mice model was associated with increased plasma and tissue Ang II levels [ 50 ], led to impaired glucose homeostasis [ 51 ] and cardiovascular damage [ 50 ].…”

“…The deletion of ACE2 in mice model was associated with increased plasma and tissue Ang II levels [ 50 ], led to impaired glucose homeostasis [ 51 ] and cardiovascular damage [ 50 ]. The molecular mechanism might be involved in posttranscriptional regulation via microRNA, because it has been reported that the changes of ACE2 expression was in protein level rather than mRNA level in diabetic mice [ 52 ], and microRNA might regulate RAAS activity via by altering the interaction between microRNA and mRNA of targeted gene [ 49 ] that need to be investigated further.…”

Association of ACE2 polymorphisms with susceptibility to essential hypertension and dyslipidemia in Xinjiang, China

“…Although the roles of ACE2 gene polymorphisms (mutations or variants) on hypertension, dyslipidemia and its related ASCVD were incompletely understood, it may be related to the cross-talk between ACE2/Ang-(1–7)/Mas axis and ACE/Ang II/AT1 axis [ 43 ]. ACE2 gene polymorphisms (e.g., rs2106809 [ 44 ], rs2074192 [ 43 ]) were associated with downregulation of circulating Ang-(1–7). The deletion of ACE2 in mice model was associated with increased circulation and tissue Ang II levels [ 45 ], led to cardiovascular damage [ 46 ].…”

COVID‐19 and renin‐angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) ‐ Is there any scientific evidence for controversy?

“…The more severe prognosis of patients of older age may also been related to distinct mechanisms, such as the age-associated decline in the molecular machinery involved in removing cytosolic DNA [98]. Also, patients with hypertension or diabetes show high rate of ACE2 genetic polymorphism that could influence ACE2 or Ang1-7 levels in the human body [64,[99][100][101]. Therefore, a negative correlation between ACE2 expression and mortality has been suggested [64].…”