Reduced high-density lipoprotein cholesterol (HDL-C) concentrations are a major risk factor for cardiovascular disease. Intense interest recently has been in identifying the genetic factors that contribute to an aberrant HDL-C phenotype. Finding genetic factors associated with low HDL-C concentrations in New Zealanders was the major aim of this study, with a similar analysis aimed at finding factors associated with high HDL-C concentrations included. The study began with an investigation of a New Zealand family with HDL-C deficiency. The proband had virtually no HDL-C, and was homozygous for an R1068H mutation in the ABCA1 gene. Nineteen relatives were recruited into the study, and an analysis aimed at finding the underlying cause for the disparate HDL-C phenotypes amongst H1068 carriers initiated.
A further investigation into HDL-C levels aimed to find other genetic factors that contribute to HDL-C in New Zealanders. Subjects were selected from those taking part in the Otago Vascular Disease study, and placed into three groups based on their HDL-C lipid measurement: low (n=154), mid (n=105), and high (n=102) HDL-C. Mutations in ABCAI and the apolipoprotein AI gene (APOAI) were identified in subjects with low HDL-C. Polymorphisms in ABCA1 and APOAI were also investigated as contributors to HDL-C concentrations. Seventeen SNPs in functionally relevant regions were genotyped in the three HDL-C groups. Five single polymorphisms and one polymorphism haplotype showed a statistically significant association with HDL-C concentrations.
The final analysis investigated plasma lipoprotein compositions in individuals with low HDL-C to identify if other lipoprotein abnormalities concurred. Individuals with HDL-C below 0.65 mmol/L were almost invariably associated with triglyceride-rich VLDL and/or triglyceride-rich LDL. This finding may have relevance for an increased atherosclerotic risk for those with low HDL-C.
| Identifer | oai:union.ndltd.org:ADTP/217750 |
| Date | January 2007 |
| Creators | Slatter, Tania Lee, n/a |
| Publisher | University of Otago. Department of Biochemistry |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://policy01.otago.ac.nz/policies/FMPro?-db=policies.fm&-format=viewpolicy.html&-lay=viewpolicy&-sortfield=Title&Type=Academic&-recid=33025&-find), Copyright Tania Lee Slatter |
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