Association of the D allele of the angiotensin I converting enzyme polymorphism with malignant vascular injury

Abstract

Aims: To determine whether there is an association between the insertion/deletion (I/D) polymorphism of the human angiotensin I converting enzyme (ACE) gene and malignant vascular injury (MVI). Methods: The polymerase chain reaction was used to genotype DNA extracted from archival, paraffin wax embedded renal biopsy material from 48 patients with MVI, made up from cases of malignant hypertension (n = 23), scleroderma (n = 10), and haemolytic uraemic syndrome (n = 15), and from whole blood samples from 191 healthy controls. Results: The D allele was found more frequently in cases of MVI than in healthy controls, (65% v 52%). Both the DD and I/D genotypes occurred significantly more frequently in patients with MVI than did the II genotype (χ 2 = 7.26, p = 0.007; and χ 2 = 4.06, p = 0.04, respectively). Conclusions: Possession of at least one copy of the D allele is associated with an increased risk of developing MVI. Our data support a dominant mode of effect for the D allele. Use of the I/D polymorphism as a genetic marker for MVI may be of value clinically in identifying at risk individuals before the development of target end organ damage. Furthermore, those at risk may benefit from early ACE inhibition.

Angiotensin‐Converting Enzyme I/D Polymorphism in Patients With Malignant Hypertension

“…However, the normal control subjects in Stefansson's study had DD genotype frequencies considerably lower than in previously reported European studies: 17.6% compared with 30% and 39% 2,19,20 . In contrast, DD frequency in our own healthy control population of 33% was close to that of a large meta‐analysis including 135 studies and 19,065 subjects with a quoted frequency of 28% 21,23,24 . This percentage is higher than that reported by Stefansson 18 and provides a more solid basis for the relationship between ACE I/D polymorphism and MH.…”

“…Although the proportion of the DD genotype in the control group of this study did not correspond to previously published percentages, 2,19,20 this series suggested that ACE gene polymorphism could be a significant risk factor for the initiation of MH. Shortly afterwards, Mayer et al 21 showed an association of the D allele of angiotensin I converting enzyme polymorphism in a variety of pathological entities with histological lesions of malignant vascular injury.…”

Angiotensin-converting enzyme gene and endothelial nitric oxide synthase gene polymorphisms in Behçet’s disease with or without ocular involvement

“…Recently no difference was found between the ACE gene alleles and the disease manifestation [16]. The recent report of the association between presence of the D allele and vascular injury in malignant hypertension, systemic sclerosis, and hemolytic uremic syndrome encouraged us to hypothesize that the development of vasculitis might have been related to the D allele in BD [24]. Ozturk et al [25] reported a finding similar to ours, in that there was no significant difference between the BD group and the controls.…”

Protective effects of angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A polymorphisms on dilatative pathology within the ascending thoracic aorta

“…D/D homozygotes were amplified again with an insertion-specific primer pair. A 335-bp PCR product only in the presence of the I allele was amplified using 5′-TGG GAC CAC AGC GCC CGC CAC TAC-3′ as sense primer and 5′-TCG CCA GCC CTC CCA TGC CCATAA-3′ as antisense primer [14]. …”