Relationship of Bradykinin B2 Receptor Gene Polymorphism with Essential Hypertension and Left Ventricular Hypertrophy

Abstract

The bradykinin B2 receptor shows a protective role in the development of hypertension and renal and cardiovascular complications. It was recently reported that a polymorphism of the bradykinin B2 receptor gene (BDKRB2) is a genetic predisposing factor for hypertension and cardiovascular disease. The aim of this study was to examine the relationship of a polymorphism (-58 T/C and exon 1 +9/-9) of BDKRB2, and an insertion/deletion polymorphism (I/D) of the angiotensin converting enzyme gene (ACE) with essential hypertension and cardiovascular mortality in the Japanese population. Genotyping was carried out in 275 hypertensive and 441 normotensive subjects. Left ventricular hypertrophy (LVH) was detected by ECG in 242 untreated patients with hypertension. All participants were Japanese and gave their written informed consent. The polymorphism (-58 T/C) in the promoter region of the BDKRB2 was determined using the TaqMan-polymerase chain reaction (PCR) method, the exon 1 +9/-9 polymorphism of the BDKRB2 and I/D polymorphism of the ACE were monitored by PCR and gel electrophoresis. The genotypes and allelic frequencies were in Hardy-Weinberg equilibrium. The polymorphism (-58 T/C) in the promoter of the BDKRB2 was associated with LVH in the hypertensive group (n =242) (p =0.048; chi2 =3.9; odds ratio: 1.8; 95% confidence interval (CI): 1.0-3.3). Furthermore, the frequency of LVH in hypertensives was significantly higher in the subjects with both the BDKRB2 CC and ACE D allele than those with other genotypes (p =0.002, chi2 =9.4). However, no relationship could be found between polymorphism of the BDKRB2 (p =0.86, chi2 =0.3) or the ACE (p =0.21, chi2 =3.1) and hypertension in this group of subjects. These results suggest that the polymorphism (-58 T/C) in the promoter region of BDKRB might be a risk factor and might have a synergetic effect with the ACE for LVH in hypertensives, but it is not associated with hypertension in the Japanese population.