Angiotensin-converting Enzyme Genetic Polymorphism

Polymorphism, Genetic; Peptidyl-Dipeptidase A

Sir Editor,

The recent report on "angiotensin-converting enzyme (ACE) genetic polymorphism." is very interesting. Albuquerque et al.¹ concluded that "the DD genotype was independently associated with worse echocardiographic outcome, while the DI genotype, with best echocardiographic profile." In fact, the polymorphism of ACE is different in different countries and the relationship to clinical disorder is widely mentioned². The study of ACE polymorphism has proved to be useful in management of cardiac patients, especially for selection of proper cardiac drug³. However, the relationship to cardiac pathology is still controversial. Similar to the present study, the ventricular function abnormality determined by EKG was proposed for interrelationship with ACE polymorphism by Yu Jin et al⁴. Nevertheless, the small sample size in the published studies^{1, 4} is the main obstacle for conclusions. The effect of race in clinical relationship of ACE polymorphism requires a very large study in order to lead to conclusions².

References

• ¹
  Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AF, et al. Angiotensin-converting enzyme genetic polymorphism. Arq Bras Cardiol. 2013 Nov 26. [Epub ahead of print].
• ²
  Wiwanitkit V. Angiotensin-converting enzyme gene polymorphism: I and D alleles from some different countries. Clin Appl Thromb Hemost. 2004;10(2):179-82.
• ³
  Yip VL, Pirmohamed M. Expanding role of pharmacogenomics in the management of cardiovascular disorders. Am J Cardiovasc Drugs. 2013;13(3):151-62.
• ⁴
  Yu Jin, Kuznetsova T, Thijs L, Richart T, Stolarz-Skrzypek K, Yanping Liu, et al. Association of echocardiographic left ventricular structure with the ACE D/I polymorphism: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011;12(3):243-53.

Reply

Indeed, the sample size limitation is a universal bias in all of the genetic polymorphisms in heart failure and the ACE-genotype was no different. The metanalysis by Bai et al.¹. with 17 different studies included 2.453 cases (i.e. heart failure patients) from all over the world with only 60.3% being white individuals. The author concluded that there was no association between ACE DD genotype and heart failure risk. The different ethnic background of these populations is one of the reasons for the lack of the association and when analyzed individually, some of these studies^2,3 did find a relation with ACE genotype and heart failure risks. Even more important is the relationship between the surrogate markers of disease progression - Echocardiogram parameters - and the genotypes since clinical outcomes will be very hard to prove with the sample size of these populations (which would have to be in thousands not hundreds). Andersson and Sylvén⁴ for example did find a relationship between echocardiographic parameteres and the ACE genetic polymorphisms. In conclusion, it looks like all these papers combined do not have statistical power to answer in a definitive way the relationship between Heart Failure Prognosis and ACE Genetic Polymorphisms. But it looks like we are on the right track and we will have to proceed with a lot more patients.

Sincerely,

Felipe Neves de Albuquerque

Andréa Araujo Brandão

Dayse Aparecida da Silva

Ricardo Mourilhe-Rocha

Gustavo Salgado Duque

Alyne Freitas Pereira Gondar

Luiza Maceira de Almeida Neves

Marcelo Imbroinise Bittencourt

Roberto Pozzan

Denilson Campos de Albuquerque

References

• ¹
  Bai Y, Wang L, Hu S, Wei Y. Association of angiotensin-converting enzyme I/D polymorphism with heart failure: a meta-analysis. Mol Cell Biochem. 2012;361(1-2):297-304.
• ²
  Candy GP, Skudicky D, Mueller UK, Woodiwiss AJ, Sliwa K, Luker F, et al. Association of left ventricular systolic performance and cavity size with angiotensin-converting enzyme genotype in idiopathic dilated cardiomyopathy. Am J Cardiol. 1999;83(5):740-4.
• ³
  Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, et al. Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet. 1993;342(8879):1073-5.
• ⁴
  Andersson B, Blange I, Sylvén C. Angiotensin-II type 1 receptor gene polymorphism and long-term survival in patients with idiopathic congestive heart failure. Eur J Heart Fail. 1999;1(4):363-9.

• Erratum

  June, 2014, edition, The letter to the Editor "Angiotensin-converting Enzyme Genetic Polymorphism", published in the June, 2014, edition of the "Arquivos Brasileiros de Neurologia"[Arq Bras Cardiol.2014; 102(6): 611-612], has been thus corrected in the reply-letter: Please add to it the signatures of the authors "Felipe Neves de Albuquerque, Andréa Araujo Brandão, Dayse Aparecida da Silva, Ricardo Mourilhe-Rocha, Gustavo Salgado Duque, Alyne Freitas Pereira Gondar, Luiza Maceira de Almeida Neves, Marcelo Imbroinise Bittencourt, Roberto Pozzan, Denilson Campos de Albuquerque."

Publication Dates

• Publication in this collection
  June 2014

History

• Received
  03 Dec 2013
• Reviewed
  23 Jan 2014
• Accepted
  23 Jan 2014