Introduction: Bradykinin, a vasodilator by nature has been documented to have a protective role against hypertension and cardiovascular complications. Polymorphisms of bradykinin B2 receptor (BDKRB2) gene are reported to be predisposing factors for hypertension. Evaluation of the association between -58C>T and ±9 bp polymorphisms of BDKRB2 with essential hypertension (EHT) was attempted.
Methods: Two hundred and fourteen primary hypertensives and 249 controls were genotyped for the selected markers by polymerase chain reaction, gel electrophoresis (±9 bp), and SSCP (-58C>T).
Results: While -58C>T polymorphism did not reveal any association with EHT, ±9 bp polymorphism showed a significant association with high risk for heterozygotes (+9/-9) when tested against the pooled frequencies of homozygotes (OR [odds ratio] = 1.63, 95% confidence interval [CI] = 1.12-2.38, P = .02), and this risk was 1.7 folds high in males (OR = 1.74, 95% CI = 1.05-2.86, P = .06) and 1.9 folds high in familial cases (OR = 1.96, 95% CI = 1.09-3.53, P = .04). In contrast, significant protective effect was observed for -9/-9 genotype against EHT when tested under dominant model in general (OR = 0.59, 95% CI = 0.41-0.86, P = .01), in males (OR = 0.49, 95% CI = 0.30-0.82, P = .01), and in familial cases (OR = 0.50, 95% CI = 0.28-0.89, P = .04). Significant risk for +9 bp allele was observed in general (OR = 1.39, 95% CI = 1.05-1.86, P = .04) and in males (OR = 1.65, 95% CI = 1.13-2.41, P = .02). The interaction information analysis revealed a synergistic effect between the two polymorphisms contributing to EHT. +9/+9 genotype of ±9 bp polymorphism when present in combination with CC genotype of -58C>T polymorphism showed 2.2-fold higher risk for developing EHT.
Conclusions: The results suggest that allele +9 bp might be a risk factor for EHT in general and specially in males. Markers -58C>T and ±9 bp may act synergistically causing susceptibility to EHT.