Genetic associations of bradykinin type 2 receptor, alpha-adrenoceptors and endothelial nitric oxide synthase with blood pressure and left ventricular mass in outpatients without overt heart disease
Publication date: December 2018
Source: IJC Heart & Vasculature, Volume 21
Author(s): Rafael Amorim Belo Nunes, Larissa Barbosa Lima, Nelson Ithiro Tanaka, Alexandre da Costa Pereira, José Eduardo Krieger, Alfredo José Mansur
Physiological pathways such as bradykinin, renin-angiotensin, neurohormones and nitric oxide have been shown to play an important role in the regulation of cardiovascular function. Genetic variants of these pathways may impact blood pressure and left ventricular (LV) mass in different populations. To evaluate associations of genetic polymorphisms of bradykinin B2 receptor (BDKRB2), alpha-adrenergic receptors (ADRA) and endothelial nitric oxide synthase (eNOS) on the modulation of the blood pressure and the left ventricular mass.
We enrolled 758 individuals without overt heart disease. Blood pressure was estimated by auscultatory method during the clinical examination. Left ventricular (LV) mass was assessed by echocardiography. Genotypes for ADRA1A rs1048101, ADRA2A rs553668, ADRA2B rs28365031, eNOS rs2070744, eNOS rs1799983, and BDKRB2 rs5810761 polymorphisms were assessed by high-resolution melting analysis.
BDKRB2 polymorphism rs5810761 was associated with blood pressure. Carriers of DD genotype had higher levels of SBP and DBP than carrier of II genotype (p = 0.013 and p = 0.007, respectively). eNOS polymorphism rs1799983 was associated with DBP. Carriers of GT genotype had lower levels of DBP than carriers of GG genotype (p = 0.018). eNOS polymorphism rs2070744 was associated with LV mass. Carriers of TC genotype had higher LV mass than carriers of TT genotype (p = 0.028).
In a cohort of individuals without overt heart disease, the BDKRB2 rs5810761 polymorphism (DD genotype carriers) were associated higher systolic and diastolic blood pressures, and the eNOS rs1799983 polymorphism (T allele carriers) were associated with lower diastolic blood pressure. The eNOS rs2070744 polymorphism (C allele carriers) was associated with higher left ventricular mass. These data suggest that eNOS and bradykinin receptor genetic variants may be potential markers of common cardiovascular phenotypes.