Association and Interaction of −58C>T and ±9 bp Polymorphisms of BDKRB2 Gene Causing Susceptibility to Essential Hypertension

Abstract

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.

• essential hypertension
• bradykinin
• bradykinin B2 receptor
• epistatic interaction

ACKNOWLEDGEMENTS

This work has been funded by University Grants Commission (UGC), New Delhi, India. The authors are thankful to all the patients and controls who voluntarily extended their cooperation in this study.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.