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Relationship Between Single Nucleotide Polymorphisms and Severe Dengue in a Brazilian Population

Kamasa-Quashie, Dzigbordi (2020) Relationship Between Single Nucleotide Polymorphisms and Severe Dengue in a Brazilian Population. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Dengue virus has become one of the most important arboviral diseases of today. With nearly half of the global population at risk, this infectious disease carries great significance. The aim of this study was to determine the relationship between 18 single nucleotide polymorphisms (SNPs) and severe dengue in a population from Recife, Brazil. The SNPs of interest are as follows: TLR8 rs17256081, IFNG rs2069718, IFNG rs2069727, IRF1 rs2070729, OAS2 rs2072137, OAS2 rs2072138, OAS3 rs2240188, MX1 rs3737399, VEPH1 rs3911403, IRAK4 rs4251580, CLEC4C rs17199006, PLCE1 rs3740360, MRC1 rs606231248, MRC1 rs2296414, RNASEL rs486907, OASL rs3213545, MX1 rs7277299, and MICB rs3132468. A total of 450 DNA samples were pulled from two studies—a cohort study of dengue patients and a yellow fever vaccine cohort. Sample concentrations were tested using the Nanodrop 1000 Spectrometer. The concentrations of all samples were between 10-100 ng/uL, per the laboratory technician’s request. Samples were transported to the University of Pittsburgh’s Genomic Core Research Laboratory for genotyping using the iPlex MassARRAY system and results were analyzed using Microsoft Excel and R statistical software. Of the 18 SNPs, statistically significant results were observed for OAS2 rs2072137, OAS3 rs2240188, PLCE1 rs3740360, and MX1 rs7277299. For OAS2 rs2072137, the CC genotype was shown to be significantly associated with severe dengue (OR=2.10, P=0.01). The CC genotype associated with OAS3 rs2240188 also appears to influence disease severity (OR=1.96, P=0.02). For PLCE1 rs3740360, calculations reveal a significant association between the AA genotype and severe dengue (OR=2.28, P=0.03). The last notable result was found in MX1 rs7277299 (OR=5.33, P=0.02) where the CC genotype was also significantly associated with severe disease. Though this is one of the largest dengue-related gene association studies, further research is necessary to validate the findings. The increasing burden of dengue disease signifies the public health importance of this research—to contribute to the advancement of dengue research, vaccine development, therapeutic strategies, and diagnostic tools.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kamasa-Quashie, Dzigbordidzk6@pitt.edudzk6
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMartinson, Jeremyjmartins@pitt.edu
Committee MemberMarques, Ernestomarques@pitt.edu
Committee MemberRussell, Joannejoanner@pitt.edu
Date: 30 July 2020
Date Type: Publication
Defense Date: 16 April 2020
Approval Date: 30 July 2020
Submission Date: 14 May 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 60
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MPH - Master of Public Health
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Dengue, polymorphism, SNP
Date Deposited: 30 Jul 2020 17:13
Last Modified: 30 Jul 2020 17:13
URI: http://d-scholarship.pitt.edu/id/eprint/39024

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