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Human and microbial genetic factors contributions to the development of HIV-associated neurocognitive disorder

Victor, Blandine (2016) Human and microbial genetic factors contributions to the development of HIV-associated neurocognitive disorder. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Years of research and the development of effective therapeutic treatments, have dramatically improved the life expectancy rates for HIV-infected individuals. However, there is a subpopulation of aging, infected individuals who have experienced an adverse impact on their long-term health and quality of life, the mechanism of which has become an increasing concern of public health importance. The counteractive outcomes of aging within the infected population leaves many susceptible to developing age related morbidities in the form of cognitive impairment, brain atrophy, and other neurocognitive disorders at an earlier age then those within the non-infected population. These symptoms manifest in the form of HIV-associated Neurocognitive Disorder or HAND in infected individuals. Fully understanding the process in which HAND can occur has been a striving goal within the Public Health community. Our goal is to determine if there are specific genetic and/or microbial factors within individuals that may be contributing to their development of cognitive decline. All these efforts could provide comprehensive insight at an endophenotypic level into the pathological mechanism of HAND, and a better understanding of how diversity in the gut microbiome can affect health and aging. Subsequently, this information could lead to the identification of genetic biomarkers, development of treatments, and therapeutic options for regulating chronic HIV infection and neuropathology. We hypothesize that inherited SNPs in genes of the folate metabolism pathway affect the availability of methyl groups within the cell, and consequently influence DNA methylation, leading to the development of HAND in seropositive individuals, and neurocognitive decline in seronegative individuals. We also hypothesize that there is an altered composition of the microbiome within the gut of infected individuals, the presence of which directs the level of HIV pathogenesis and HAND development. In comparing HIV+ and Cognitive Decline groups against control groups, we do not have sufficient evidence to conclude that there is an increased risk of adverse outcome in association with any of the folate genes that we observed. Isolation of bacterial genome produced expected PCR product, and data interpretation following 16S rRNA sequencing will soon yield definitive microbial composition analysis.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Victor, Blandinebfv1@pitt.eduBFV1
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorMartinson, Jeremy Jjmartins@pitt.eduJMARTINS
Committee MemberHartman, Amyhartman2@pitt.eduHARTMAN2
Committee MemberBecker, James T.beckerjt@upmc.eduBECKERJT
Date: 29 June 2016
Date Type: Publication
Defense Date: 25 April 2016
Approval Date: 29 June 2016
Submission Date: 31 March 2016
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 69
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: HAND, DNA Methylation, Microbial Composition, Accelerated Aging
Date Deposited: 29 Jun 2016 18:47
Last Modified: 19 Dec 2016 14:43
URI: http://d-scholarship.pitt.edu/id/eprint/27466

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