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Folate Metabolism Genetic Variation and Heart Disease Risk in HIV+ Men Undergoing Antiretroviral Therapy

Mamo, Anna Jean (2010) Folate Metabolism Genetic Variation and Heart Disease Risk in HIV+ Men Undergoing Antiretroviral Therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

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 individual's 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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Mamo, Anna Jeanannamamo1@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMartinson, Jeremyjmartins@pitt.eduJMARTINS
Committee MemberKammerer, Candacecmk3@pitt.eduCMK3
Committee MemberReinhart, Toddreinhar@pitt.eduREINHAR
Date: 28 June 2010
Date Type: Completion
Defense Date: 22 April 2010
Approval Date: 28 June 2010
Submission Date: 12 April 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Cardiovascular Disease; SNPs; HAART; HIV
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04122010-160019/, etd-04122010-160019
Date Deposited: 10 Nov 2011 19:36
Last Modified: 15 Nov 2016 13:39
URI: http://d-scholarship.pitt.edu/id/eprint/7072

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