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Title: Telomeres and coronary heart disease
Author: Brouilette, Scott Wayne
ISNI:       0000 0001 3482 6474
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2004
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Using mean telomere length as a marker of biological age, I show that: 1. Subjects with premature myocardial infarction (MI) have significantly shorter telomeres than age-sex matched, healthy, controls. The mean telomere length in MI subjects was similar to controls almost 11 years older. 2. Healthy young adult children of families with a strong history of premature MI have shorter telomeres than age matched children of families without such a history. 3. Shorter telomere lengths are associated with increase risk of subsequent CHD events in a prospective study. This analysis was carried out on samples collected in the West of Scotland Coronary Prevention Study (WOSCOPS). This randomised blinded trial was designated to examine the benefits of statin treatment on preventing CHD and showed a 30% reduction of events in those treated with pravastatin. Interestingly, my analysis showed that this benefit of statin is only seen in those subjects at higher risk of CHD based on their telomere length.;As the final part of the thesis I carried out a quantitative linkage trait (QTL) analysis in sib-pairs in an attempt to identify genetic loci regulating telomere length. I report the mapping of a major QTL on chromosome 12 that determines almost 50% of the inter-individual variation in mean telomere length.;These findings support a novel "telomere" hypothesis of CHD. They indicate that telomere biology is intimately linked to the genetic aetiology and pathogenesis of CHD. Specifically, the findings suggest that (i) those individuals born with shorter telomeres may be at increased risk of CHD (ii) rather than individual genes, a more global structural property of the genetic material may explain the familial basis of CHD (iii) variation in telomere length may explain, in part, the variable age of onset of CHD. The findings provide several new avenues for future research.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available