Coronary heart disease (CHD) is a major public health problem in western countries as it continues to be a leading cause of premature mortality and morbidity. Several risk factors contribute to CHD risk, including dyslipidemia with low high density lipoprotein cholesterol (HDL-C) and high low density lipoprotein cholesterol (LDL-C). Meta analysis of genome wide linkage analysis in families with diverse ethnicity has revealed a strong linkage with different lipid traits on chromosome 19q13.2. There are several candidate genes present under this linkage region, including APOE/C1/C4/C2 gene cluster. With the exception of APOE, other genes in this cluster have not been extensively evaluated in relation to lipid profile. Therefore, identifying APOC4 genetic variants that modulate HDL-C level is a great public health importance. In this study we focused on the APOC4 gene and hypothesized that rare and common variants in this gene could affect plasma lipid levels. Integration of common variants common disease (CVCD) and rare variants common disease (RVCD) hypotheses has been conducted in a limited number of studies. The aim of this study was to identify both common and rare variants in APOC4 by sequencing individuals having extreme low and high HDL-C levels from U.S. non-Hispanic Whites (NHWs) and African Blacks, and to examine their effects on HDL-C and correlated lipid levels. In the sequencing analysis, a total of 65 variants were identified in NHWs and African Blacks. Of these 26 were present in NHWs and 51 in Blacks. Among NHWs, 31% of the low HDL-C group had rare or less common variants versus 10% of the high HDL-C group. On the other hand, reverse trend was observed in the Black sample (46% of the low HDL-C group versus 54% of the high HDL-C). Screening of these observed rare and common variants in the complete NHWs and Blacks dataset would provide more information about their association with plasma HDL-C and correlated lipid traits.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-11302010-103708 |
| Date | 31 January 2011 |
| Creators | Radwan, Zaheda Hassan |
| Contributors | F. Yesim Demirci, Clareann H. Bunker, M. Ilyas Kamboh |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-11302010-103708/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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