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Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/8737

Title: A Haplotype Analysis of the Angiotensin Converting Enzyme Gene in Ischaemic Stroke
Authors: Dennis, Gary Jon
Supervisors: Abbott, R.J.
Trembath, R.
Award date: 4-Jul-2008
Presented at: University of Leicester
Abstract: Background: Epidemiological studies lend some support for a genetic predisposition to human stroke. There is a growing body of evidence to suggest a role for Angiotensin II (ANGII) in vascular disease. The levels of Angiotensin converting enzyme (ACE), which converts ANGI to ANGII, are known to be under a significant degree of genetic control. The D allele of the ACE I/D polymorphism is associated with higher serum ACE levels and this allele has also been associated with ischaemic stroke. Recent identification of numerous ACE single nucleotide polymorphisms has allowed for a more powerful case control haplotype analysis of ACE in ischaemic stroke. Patients and Methods: The validity of the published structure of the common ACE haplotypes was investigated and supported using long range allele specific PCR and DNA sequencing of a random sample of UK caucasian subjects. Using restriction fragment length polymorphism (RFLP) analysis of selected polymorphisms we generated ACE haplotypes for 359 ischaemic stroke patients and 328 unrelated controls. Results: Age, hypertension, smoking, diabetes and hypercholesterolaemia were identified as significant clinical risk factors for ischaemic stroke. D allele frequencies showed no significant differences between cases and controls (0.55 vs 0.53 respectively). However a low frequency D allele haplotype (H9) was found to be an independent risk factor for ischaemic stroke (odds ratio 2.05, p=0.004). Conclusion: This study has provided allele specific data to support the haplotype structure of the common ACE haplotypes in a UK caucasian population. For the first time, in a case control analysis, we have identified a significant and independent genetic association of a low frequency ACE haplotype, H9, with human ischaemic stroke. This result suggests an important role for ACE in ischaemic stroke which will require further study in other populations using a variety of control groups.
Links: http://hdl.handle.net/2381/8737
Type: Thesis
Level: Doctoral
Qualification: MD
Appears in Collections:Theses, Dept. of Cardiovascular Sciences
Leicester Theses

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