Background - The Martinson Lab is examining genetic characteristics related to cardiovascular disease (CVD) in men with HIV undergoing HAART therapy that are enrolled in the Multicenter Aids Cohort Study (MACS). CVD is a major side effect of HIV infection and HAART therapy. While the mechanism behind this remains unknown, the folic acid metabolic pathway may be involved. This study examines genes that encode enzymes involved in this pathway. Polymorphisms in these genes may lead to increased risk of CVD due to altered function of the enzymes they encode. The following polymorphisms in the MTHFR, MS, and MTRR genes have been found to affect enzymatic function of Methylenetetrahydrofolate reductase (MTHFR), Methionine Synthase (MS or MTR), and Methionine Synthase Reductase (MTRR) respectively: MTHFR C677T, MTHFR C1068T, MS A2756G and MTRR A66G. SNP genotypes for these loci were characterized for the MACS DNA samples. These results were compared with corresponding clinical data and statistics were used to determine how polymorphisms affect cardiovascular disease when influenced by HIV infection and HAART therapy. Methods MACS DNA samples were amplified using PCR, and each SNP was characterized using a Fluorescence Polarization Assay (FP). These data and clinical data for LDL, HDL, triglyceride, BMI, HIV status, HAART status, age, gender, and family history were analyzed using box-and-whisker diagrams, Kruskal-Wallis test, odds ratio calculations, and logistic regression analysis. Results Visual trends were seen between LDL levels and polymorphisms in MTHFR C1068T and MS A2756G. However, no significant associations were found statistically between SNP genotypes and LDL levels. A protective association may exist between the MS A2756G GG genotype and not-high LDL levels, but the small sample size of this genotype means that statistical significance was not reached. We intend to obtain data for more samples and repeat statistical calculations. This may lead to statistically significant outcomes. This thesis contributes to public health by furthering knowledge of how an individuals genetics influences CVD risk while being HIV+ and undergoing HAART therapy. This knowledge enables the patient to be given the best care possible with regards to their individual situations.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04122010-160019 |
| Date | 28 June 2010 |
| Creators | Mamo, Anna Jean |
| Contributors | Dr. Jeremy Martinson, Dr. Todd Reinhart, Dr. Candace Kammerer |
| 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-04122010-160019/ |
| Rights | unrestricted, 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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