Heart disease (HD) is a primary public health concern, with HD being one of the leading causes of death every year in the United States. Many risk factors influence HD, including lipid levels, and studies have shown that higher levels of plasma high density lipoprotein (HDL) cholesterol have a protective effect against HD. Recent genome-wide linkage scans have associated a locus on chromosome 7, harboring CD36, as being involved in components of the metabolic syndrome, including HDL-C levels. Therefore, identifying variation in this gene affecting HDL-C levels is of great public health importance. The "common variant-common disease" hypothesis has been tested by a limited number of studies through common SNP genotyping with inconsistent results. To date, no studies to our knowledge have evaluated CD36 using the "rare variant-common disease" hypothesis. The aim of this study was to further evaluate the role of common and rare variation in CD36 by sequencing individuals having extremely low and high HDL-cholesterol levels in two populations, U.S. Non-Hispanic Whites (NHWs), and African Blacks. In our initial sequence analysis, 343 variants were identified in CD36, 168 of which were previously unreported in the SeattleSNPs database. According to preliminary analysis of the sequencing data, our findings support the associations of three SNPs with HDL-C levels reported in the literature. No striking difference was noticed between the distribution of rare variants between high and low HDL-C groups. We identified four common variants (MAF ≥ 5%) in our sequencing data from our small sample that displayed statistically significant differences in MAF between the low and high HDL-C groups but have not been confirmed yet by genotyping in the entire NHW and Black populations while thirteen common variants had p-values between 5-10%, which may be statistically significant due to the small sample size. To date, screening data was compiled for the entire NHWs and Black samples for a total of nineteen common variants. None of these variants displayed a significant p-value in our entire NHW and Black samples. Additional variants identified in sequencing remain to be screened in the entire NHW and Black samples.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04052010-143451 |
| Date | 29 June 2010 |
| Creators | Hughes, Sarah Caitlin |
| Contributors | F. Yesim Demirci, David N. Finegold, 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-04052010-143451/ |
| 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. |
Page generated in 0.0031 seconds