Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Letter
  • Published:

Insertion/deletion polymorphism of the bradykinin type 2 receptor gene influence diastolic blood pressure

Journal of Human Hypertension volume 23, pages 553–555 (2009)Cite this article

The contribution of kinins to the beneficial effects in cardiovascular risk reductions remains unclear. In this context, the present study examined whether the +9 bp/−9 bp polymorphism in bradykinin type 2 receptor gene, predicts hypertension risk in a large urban Brazilian population. Our finding indicated that the −9 bp allele may contribute to hypertension because of increased diastolic pressure.

Bradykinin, acting through its type 2 receptor (B2R), exerts significant vascular protective effects including the stimulation of microangiogenesis, inhibition of smooth muscle cell growth, coronary vasodilatation, increased local nitric oxide synthesis and anti-thrombotic actions.1 The cardioprotective effects of angiotensin-converting enzyme inhibitors derive in part from the capacity of these agents to enhance the beneficial contributions of the bradykinin and B2R.1 The role of bradykinin in health and disease has been highlighted by recent studies that have identified associations between genetic variations in the B2R and significantly higher coronary risk attributable to hypertension2 and decreased regression of left ventricular mass in response to antihypertensive treatment.3 These studies have focused in a functional polymorphism described in exon 1 of the bradykinin type 2 receptor gene (BDKRB2),4 in which the presence (+9 bp) rather than the absence (−9 bp) of a 9-base pair sequence was associated with lower gene transcriptional activity.5, 6 If raised kinin activity is indeed vascular protective, we would anticipate that low bradykinin receptor activity, as marked by the +9 bp allele, would be associated with increased cardiovascular risk. According with these facts, the present study aimed to evaluate whether +9 bp/−9 bp polymorphism was associated with blood pressure (BP) variation on an admixture urban population.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Sharma JN . Does the Kinin System Mediate in Cardiovascular Abnormalities? An Overview. J Clin Pharmacol 2003; 43: 1187–1195.

    Article  CAS  Google Scholar 

  2. Dhamrait SS, Payne JR, Li P, Jones A, Toor IS, Cooper JA et al. Variation in bradykinin receptor genes increases the cardiovascular risk associated with hypertension. Eur Heart J 2003; 24: 1672–1680.

    Article  CAS  Google Scholar 

  3. Hallberg P, Lind L, Michaelsson K, Karlsson J, Kurland L, Kahan T et al. B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. J Hypertens 2003; 21: 621–624.

    Article  CAS  Google Scholar 

  4. Braun A, Kemmerer S, Böhme E, Muller B, Roscher AA . Identification of polymorphic sites of the human bradykinin B2 receptor site. Biochem Biophys Res Commun 1995; 211(1): 234–240.

    Article  CAS  Google Scholar 

  5. Braun A, Kemmerer S, Maier E, Böhme E, Roscher AA . Polymorphisms in the gene for the human B2-bradykinin receptor. New tools in assessing a genetic risk for bradykinin-associated diseases. Immunopharmacology 1996; 33: 32–35.

    Article  CAS  Google Scholar 

  6. Lung CC, Chan EK, Zuraw BL . Analysis of an exon 1 polymorphism of the B2 bradykinin receptor gene and its transcript in normal subjects and patients with C1 inhibitor deficiency. J Allergy Clin Immunol 1997; 99: 134–146.

    CAS  PubMed  Google Scholar 

  7. The World Health Organization MONICA Project (monitoring trends and determinants in cardiovascular disease): a major international collaboration. WHO MONICA Project Principal Investigators. J Clin Epidemiol 1988; 41: 105–114.

    Article  Google Scholar 

  8. Miller SA, Dykes DD, Polesky HF . A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

    Article  CAS  Google Scholar 

  9. Kemmerer S, Braun A, Arnold N, Roscher AA . The human bradykinin 2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region. Biochem Biophys Res Commun 1995; 221: 226–233.

    Article  Google Scholar 

  10. Pretorious MM, Gainer JV, Van Guilder GP, Coelho EB, Luther JM, Fong P, Rosenbaum DD et al. The bradykinin type 2 receptor BE1 polymorphism and ethnicity influence systolic blood pressure and vascular resistance. Clin Pharmacol Ther 2008; 83 (1): 122–129.

    Article  Google Scholar 

  11. Cui J, Melista E, Chazaro I, Zhang Y, Zhou X, Manolis AJ, Baldwin CT et al. Sequence variation of bradykinin receptors B1 and B2 and association with hypertension. J Hypertens 2005; 23: 55–62.

    Article  CAS  Google Scholar 

  12. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. National Heart LaBIJNCoPDEaToHBP, National High Blood Pressure Education Program Coordinating C. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. (see comment)(erratum appears in JAMA, 2003 July 9; 290(2):197). JAMA 2003; 289: 2560–2572.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Genetics and Molecular Cardiology, Heart Institute/InCor, University of São Paulo Medical School, São Paulo, Brazil

    S R Freitas, A C Pereira, M S Floriano & J E Krieger

  2. Laboratory of Human Genetics, Oswaldo Cruz Institute/FIOCRUZ, Rio de Janeiro, Brazil

    S R Freitas

  3. Department of Physiology, Espírito Santo Federal University, Vitória, Brazil

    J G Mill

Authors
  1. S R Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A C Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M S Floriano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J G Mill
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J E Krieger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A C Pereira.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Freitas, S., Pereira, A., Floriano, M. et al. Insertion/deletion polymorphism of the bradykinin type 2 receptor gene influence diastolic blood pressure. J Hum Hypertens 23, 553–555 (2009). https://doi.org/10.1038/jhh.2009.23

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2009.23

Search

Advanced search

Quick links