The angiotensinogen gene 235T variant is associated with an increased risk of restenosis after percutaneous transluminal coronary angioplasty

Abstract

The therapeutic benefit of percutaneous transluminal coronary angioplasty (PTCA) is limited by restenosis in 30-40% of patients. The underlying mechanisms are currently not well understood. Besides clinical and angiographic variables, genetic factors may be involved. In the present study, we investigated the associations between the angiotensinogen T174M and M235T, the angiotensin I-converting enzyme (ACE) I/D and the angiotensin II type 1 receptor A1166C gene polymorphisms and restenosis in 511 patients who had undergone successful PTCA (without stenting) and follow-up angiography. Clinical and angiographic variables were also considered as possible predictors of restenosis. Stenosis severity was estimated by visual inspection of the angiograms. Altogether, 160 patients had restenosis, as defined by a greater than 50% reduction in the diameter of the dilated segment at follow-up angiography compared with the findings immediately following angioplasty. There were significantly more carriers of the angiotensinogen 235T allele and more patients with the ACE DD genotype in the restenosis group than in the no restenosis group, but only the angiotensinogen 235T allele (and not the ACE DD genotype) remained significantly associated with restenosis following multifactorial analyses. No differences between the two groups were found with respect to the other gene polymorphisms. Patients who subsequently developed restenosis had a higher degree of stenosis and more severe lesions before PTCA, as well as less residual stenosis immediately after PTCA. We conclude that the angiotensinogen M235T gene polymorphism may be an independent predictor of restenosis after PTCA.

Is AV Fistula Patency Associated with Angiotensin-Converting Enzyme (ACE) Polymorphism and ACE Inhibitor Intake?

“…Patients who bear the DD genotype of the ACE gene and who are thus genetically prone to increased ACE activity [14] were initially suggested to have a greater risk of restenosis after percutaneous coronary angioplasty compared to patients with the ID or II genotype [21]. However, larger and more rigorous studies [22][23][24] found weaker associations between the ACE DD genotype and restenosis after percutaneous coronary angioplasty, with or without additional stenting. In accordance, a meta-analysis reported an inverse correlation between study population size and magnitude of relative risk associated with I/D polymorphism [25].…”

Present status of outcome prediction of invasive coronary treatment by using genetic markers

“…In the initial study [Völzke et al, 2000], carriers of the c.803C variant had an odds ratio for developing restenosis after PTCA of 1.43 (95% confidence interval 1.06-1.93) when compared to c.803TT homozygotes. The association of the c.803C variant with an increased risk of restenosis was corroborated in a follow-up study [Hertwig et al, 2002] involving all those patients from the previous study [Völzke et al, 2000] who had suffered from restenosis and were consecutively subjected to a second PTCA procedure. In the follow-up study [Hertwig et al, 2002] carriers of the c.803C variant had an odds ratio for developing recurrent restenosis after repeated PTCA of 2.56 (95% confidence interval 1.11-5.89) when compared to TT homozygotes.…”

“…However, most of the studies were relatively small and had a limited statistical power to detect a true relation. More recently, a study [Völzke et al, 2000] comprising 511 patients found restenosis in 23% of patients with the ACE Ã I/I genotype, 32% of patients with the ACE Ã I/D genotype and 38% of patients with the ACE Ã D/D genotype. While these data are reminiscent of a gene-dose effect for the D allele, the relation between the I/D sequence variation in the ACE gene and the risk of restenosis did not attain statistical significance after adjustments for confounders had been performed.…”

“…In two consecutive studies [Völzke et al, 2000;Hertwig et al, 2002] the rare AGT c.803C variant was identified as an independent risk factor for restenosis after PTCA [Völzke et al, 2000] and for recurrent restenosis after repeated PTCA [Hertwig et al, 2002]. In the initial study [Völzke et al, 2000], carriers of the c.803C variant had an odds ratio for developing restenosis after PTCA of 1.43 (95% confidence interval 1.06-1.93) when compared to c.803TT homozygotes.…”

“…The gene coding for the AT1R (AGTR1) contains a single nucleotide sequence variation (c.1166A4C) in the 3 0 -untranslated region, which has been reported to be associated with essential hypertension [Bonnardeaux et al, 1994]. While several studies [Völzke et al, 2000;Hertwig et al, 2002;Hamon et al, 1998;Okamura et al, 1999] failed to demonstrate an association between this sequence variation and restenosis after PTCA, one study [Völzke et al, 2005] reported that the sequence variation may modulate the effects of age on total mortality after CABG surgery.…”