Jamshidi, Yalda;
(2001)
Role of PPAR[alpha] in coronary heart disease and cardiac hypertrophy.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The work presented is an investigation of the effects of polymorphisms in the peroxisome proliferator activated receptor [alpha] (PPAR[alpha]) gene on lipid metabolism, hypertrophy and atherosclerosis. The PPAR[alpha] gene-coding region was screened by single-strand conformation polymorphism analysis. Two novel variants were identified, a missense mutation changing codon 227 from valine to alanine (V227A) and a variant in the 3' untranslated region. Both polymorphisms were infrequent and neither showed any association with plasma lipid concentrations nor coronary artery disease. The effect of previously identified common variation in the PPAR[alpha] gene and promoters of fibrate-responsive genes on plasma lipid levels and response to fibrate treatment was examined in the LEADER trial, a randomised placebo-controlled trial examining the effect of bezafibrate treatment on ischemic heart disease and stroke in 800 patients suffering from lower extremity arterial disease. Variation in the PPAR[alpha] gene was associated with plasma lipid levels at baseline but not at follow-up time points, and was only mildly associated with the degree of change in plasma lipid and fibrinogen levels in response to bezafibrate treatment. The role of PPAR[alpha] in exercise-induced cardiac hypertrophy was investigated in a sample of British army recruits. The PPAR? intron 7 polymorphism was found to influence change in left ventricular mass during exercise training. The influence of the PPAR[alpha] intron 7 polymorphism on risk of ischemic events was examined in the second Northwick Park Heart Study, a prospective study of 3000 healthy middle-aged men and the rare allele of the PPAR[alpha] intron 7 polymorphism was associated with increased risk of heart disease. Finally, Real-time quantitative RT-PCR of human leukocyte derived RNA was carried out in order to determine whether the intron 7 polymorphism is associated with alterations in PPAR[alpha] gene expression, and correlate with the results observed in the LVH study.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Role of PPAR[alpha] in coronary heart disease and cardiac hypertrophy |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Health and environmental sciences; Atheroclerosis; Hypertrophy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10105260 |
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