ACE I/D Gene Polymorphism in Children with Family History of Premature Coronary Disease.

Letter to the editor regarding the article by de Albuquerque et al: Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.

I read with interest the recent review article by de Albuquerque et al[1] published in the Arquivos Brasileiros de Cardiologia entitled “Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling.” They showed that the DD genotype of Angiotensin-converting enzyme (ACE) gene polymorphism was independently associated with worse echocardiographic outcome, while the DI genotype, with the best echocardiographic profile[1].

Atherosclerosis, the major cause of CAD, manifests clinically in adulthood. However, this disease begins very early in life, often during childhood. Genetic and environmental factors, gene–environment interaction effects also come into play in the development of atherosclerosis. Family history is the most significant independent risk factor for CAD.

In our study, we included a total of 140 children, 72 males and 68 females between the ages of 4.9 and 15.7 years. Among these children, 73 had a parental history of premature CAD (parents have been diagnosed with the CAD by coronary angiographic study, ages below 55 for men and 65 for women) and the rest of 67 belonged to our control group (parents have shown normal coronary angiographic study). The participants were screened for the mutations ACE I/D gene polymorphisms.

The genotypes of ACE I/D were significantly different between the study and control groups (p = 0.01). The frequency of D/D genotype was significantly higher in the study group than the control group (respectively, 20/73 vs. 3/67, p = 0.01) (Table 1). The frequency of the D allele was slightly higher in study group (0.52) than in control group (0.27) (p = 0.005).

Table 1

The frequencies of the ACE I/D gene polymorphisms in study group and control group, and the odds ratios with 95% CI

Genetic polymorphism	Study group (Children whose parents with premature CAD) n (%)	Control group (Children whose parents without premature CAD) n (%)	p Value	Odds Ratios (CI 95%)
ACE
D/D	20 (27.4%)	3 (4.4%)	0.01	2.98 (1.12 - 6.82)[1]
D/I	37 (50.6%)	30 (44.6%)
I/I	16 (21.9%)	34 (50.0%)

: D/D versus I/D and I/I.

The angiotensin converting enzyme is a key factor in the production of angiotensin II and in the degradation of bradykinin. Chronic exposure to high levels of circulating and tissue ACE predispose to vascular wall thickening and atherosclerosis. The ACE insertion/deletion (I/D) polymorphism results from the absence or presence of an alu repeat located in intron 16 of the ACE gene. The D allele of an insertion/deletion (I/D) polymorphism of the gene encoding ACE is associated with higher plasma ACE concentrations[2]. Many studies have investigated the association between the DD genotype of ACE gene I/D polymorphic variant and CAD[3,4]. However, these outcomes have not been supported by the other studies[5]. In present study, the frequencies of D/D genotype and D allel of ACE gene considerably higher in children with parental history of premature CAD than control group.

We showed that the frequencies of the DD genotype and the D allel of ACE I/D gene polymorphism are higher in children with parental history of premature CAD. This results may be associated with an increased risk for development of atherosclerosis. It may be contribute to the detection of the risk of children with a parental history of CAD. Thus, further large population studies must be done to confirm this results.

The study protocol was approved by the Local Ethical Committee of Celal Bayar University, and informed written consent was obtained from all participants. This study was funded by Celal Bayar University.

Additional information:

In addition to ACE I/D gene polymorphism, glycoprotein IIIa, factor V G1691A, factor V H1299R, prothrombin G20210A and apolipoprotein E polymorphism had been investigated in the same study group. These results were published in various journals.

* Ciftdoğan DY. Glycoprotein IIIa gene polymorphism in children with a family history of premature coronary artery disease. Acta Cardiol. 2010 Dec;65(6):695; author reply 695-6.

** Ciftdoğan DY, Coşkun S, Ulman C, Tikiz H. The factor V G1691A, factor V H1299R, prothrombin G20210A polymorphisms in children with family history of premature coronary artery disease. Coron Artery Dis. 2009 Nov;20(7):435-9. doi: 10.1097/MCA.0b013e32832bdb8c.

*** Ciftdoğan DY, Coskun S, Ulman C, Tıkız H. The association of apolipoprotein E polymorphism and lipid levels in children with a family history of premature coronary artery disease. J Clin Lipidol. 2012 Jan-Feb;6(1):81-7. doi: 10.1016/j.jacl.2011.06.017. Epub 2011 Jul 30.