The present study was undertaken primarily to determine the prevalence of ABCA1 gene defects in a selected population with a HDL-C < 5 th percentile. The results showed that 30% of the selected patients had a lipid efflux defect and 16% (10/64) of those patients had a mutation in the ABCA1 gene. The cholesterol and phospholipid efflux showed a high correlation with HDL-C levels. In addition, both phospholipid and cholesterol effluxes (r = 0.64 p < 0.001 and r = 0.48 p < 0.001, respectively) were significantly correlated to HDL-C levels in selected hypoalphalipoproteinemia subjects. / Knowing that ABCA1 is regulated by cholesterol, oxysterols, and cAMP in peripheral cells, it was also of interest to investigate the regulation in other cells where cholesterol metabolism is an important function. Therefore the second objective was to determine the regulation of ABCA1 in hepatocytes. The results demonstrated that ABCA1 was not regulated in HepG2 cells but strongly regulated in fibroblasts. / Taken together, these studies support the two-step hypothesis proposed by Fielding et al. These studies also suggest that ABCA1 regulation in the liver is different than in peripheral cells. We believe that understanding the ABCA1 pathway will lead to a better comprehension of the reverse cholesterol transport system.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.78247 |
| Date | January 2002 |
| Creators | Bissonnette, Rachel |
| Contributors | Genest, Jacques, Jr. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001976418, proquestno: AAIMQ88155, Theses scanned by UMI/ProQuest. |
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