All ETDs from UAB

Advisory Committee Chair

Sadeep Shrestha

Advisory Committee Members

Molly S Bray

Emily B Levitan

Michael S Saag

Hemant K Tiwari

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) School of Public Health

Abstract

This dissertation research focuses on how variants in various host genes are associated with clearance of HPV in three longitudinal cohorts from the United States. I first examined the definition of the intermediate phenotype to cervical cancer, HPV persistence and then I incorporated this phenotype in all my three aims by examining variations in xenobiotic metabolism genes in HIV-1 negative and immune-related genes in HIV-1 positive females and how these contribute to HPV infection outcomes. Several significant variants were associated with HPV clearance for the three aims. For the first aim, in ALTS assessing functional variants within xenobiotic metabolism genes and clearance of HR-HPV, I observed a functional variant allele in CYP1A1 was significantly associated with lower clearance rates of HR-HPV and the GSTM1 null variant was significantly associated with higher clearance rates of HR-HPV (Chapter 3). In the second aim, using the REACH cohort assessing SNPs within Interleukin family of cytokines and Toll-like Receptors (TLRs) and their influence on HR-HPV clearance, I observed HR-HPV clearance rates were significantly associated with five SNPs that mapped to coding and regulatory regions in three genes (IL2RB, IL1RN, and IL7R) (Chapter 4). Finally in the third aim, using the HERS cohort assessing SNPs within several immune related genes and their influence on HR-HPV, I observed several significant associations between SNPs, specifically those located on chromosome 6 in the HLA-G region was associated with higher clearance rates (Chapter 5). Host genetic factors associated with higher clearance rates of HR-HPV could serve as potential biomarkers for future HPV related disease. Also, identification of susceptibility loci may allow earlier diagnosis based on an individual's genetic constitution and may facilitate identification of disease subtypes amenable to therapeutic approaches.

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