Association of Angiotensin Converting Enzyme Insertion/Deletion Polymorphism with Vaso-occlusive Complications of Sickle Cell Anaemia

Abstract

Background : Angiotensin I-converting enzyme (ACE), dipeptidyl peptidase, is a membrane-hound enzyme, which is present in endothelial and epithelial cells of various tissues, and innards including lungs and kidneys. ACE converts angiotensin I to H, a very potent vasoconstrictor agent . Angiotensin is a hormone as well as a locally produced cellular factor, directly affecting vascular endothelial cells and smooth muscles. Furthermore, it has been demonstrated that receptors of angiotensin II are found in the atherosclerotie vessel walls. It is pointed out that angiotensin II can promote vasoconstriction, inflammation, and thrombosis in the vascular endothelium and vessel walls. Besides being a potent vasoconstrictor, angiotensin Il is a proatherogenic agent, which elevates plasminogen activator inhibitor-l levels, which results in a decrease in the fibrinolytic activityhe ACE I/D polymorphism is an insertion/deletion of an ALU-repeat sequence of 287 base pairs (hp) in intron 16 of the ACE gene, located at l7q23. This results in three genotypes: II, ID, and DD.] Previous studies have reported that plasma levels of angiotensin II are closely associated with ACE insertion/deletion (I/D) polymorphism and that the serum level of ACE is likely to increase 2-fold in the presence of ACE D/D polymorphism, consequently increasing the levels of plasma angiotensin H.

Objectives: This study aimed to determine the frequency of ACE genotypes (II/ID/DD) in Sudanese patients with SCA and correlate these genotypes with disease complications. Materials and methods: A total of 50 patients with SCA and 40 healthy volunteers as a control group were enrolled in this study. Three milliliters of ethylenediamine tetraacetic acid anticoagulated blood were collected from each subject, DNA was extracted by salting-out method, and target DNA regions of the ACE gene were amplified using allele-specific polymerase chain reaction. Data of this study was analyzed by Statistical Package for Social Sciences. Frequency of qualitative variables was calculated, and correlation was tested by Chi-square test. Regression was used to investigate the association between the polymorphism and complications of SCA. Results: The frequencies of the DD, ID, and II genotypes were 42%, 50%, and 8%, respectively, for patients, whereas in the control group, it was 80% for DD genotype and 20% for ID, while II genotype was totally absent. The regression analysis showed no statistically significant association between the disease complications and each of the ACE polymorphic genotypes. Conclusion: No statistically significant association was found between ACE polymorphism and complications of SCA.