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Role of Mycobacterium avium paratuberculosis (MAP) and TNFSF15 SNPs on TL1A in CD
Title
Role of Mycobacterium avium paratuberculosis (MAP) and TNFSF15 SNPs on TL1A in CD.
Creator
Hassouneh, Sayf Al-Deen, Naser, Saleh, Yooseph, Shibu, Parthasarathy, Sampath, University of Central Florida
Abstract / Description
Tumor Necrosis Factor-Like Ligand 1a (TL1A) is a cytokine encoded by Tumor Necrosis Factor Super Family 15 gene (TNFSF15) gene mostly in endothelial cells which binds to T-cells and foments the production of pro-inflammatory cytokines including TNF-?, IL-6, IL-1b, IFN- ? and IL-13. TL1A level is elevated in inflammatory diseases including Crohn's Disease (CD). Although Single Nucleotide Polymorphisms (SNPs) in TNFSF15 have been reported in CD, no studies have investigated the effect of these...
Show moreTumor Necrosis Factor-Like Ligand 1a (TL1A) is a cytokine encoded by Tumor Necrosis Factor Super Family 15 gene (TNFSF15) gene mostly in endothelial cells which binds to T-cells and foments the production of pro-inflammatory cytokines including TNF-?, IL-6, IL-1b, IFN- ? and IL-13. TL1A level is elevated in inflammatory diseases including Crohn's Disease (CD). Although Single Nucleotide Polymorphisms (SNPs) in TNFSF15 have been reported in CD, no studies have investigated the effect of these SNPs on TL1A, inflammation, and susceptibility to Mycobacterium avium subspecies paratuberculosis (MAP) infection. MAP is a strong candidate in CD pathogenesis. This study is designed to elucidate the combined effect of MAP and SNPs in TNFSF15 (rs4263839, rs7848647, rs6478108, or rs6478109) on TL1A secretion and downstream effect on pro-inflammatory cytokines. Peripheral blood from CD and healthy subjects was analyzed for MAP DNA, TNFSF15 genotyping, circulating TL1A level, and IFN- ? and TNF-? gene expression. Our data is first to report that rs4263839, rs7848647, rs6478108, and rs6478109 in TNFSF15 resulted in increase in circulating TL1A level in healthy and CD samples. Specifically, in CD samples with rs7848647, the average TL1A level was 146.9 pg/mL (&)#177; 124.5 compared 62.4 pg/mL (&)#177; 82.8 in normal samples. Similarly, TL1A level in CD samples with rs6478109 was 141.9 pg/mL (&)#177; 127.7 compared to 71.5 pg/mL (&)#177; 88.4 in normal samples (p(<)0.05). All 4 SNPs resulted in significant elevation in TL1A level in healthy samples (p(<)0.05). Moreover, IFN-? expression was significantly higher, by approximately 1.6-fold in CD patients with SNPs relative to CD patients with no SNPs (p(<)0.05). Interestingly, SNPs in TNFS15 had no significant effect on TNF-? expression. MAP was detected in the blood of 63% of CD compared to 6% healthy subjects (p(<).001). The data did not support a correlation between MAP presence and circulating TL1A levels, and no correlation between SNPs in TNSF15 and MAP susceptibility. This study strongly suggests, that SNPs in TNFSF15 increase TL1A levels and may be a contributory factor to the inflammation experienced by CD patients. Over all, the study emphasizes the need for a pharmacogenomic approach in treatment delivery for patients with CD by using TNFSF15 SNPs to identify patients that would benefit from biologics targeting TL1A rather than TNF-? for more efficacious treatment regiments for CD patients.
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Date Issued
2018
Identifier
CFE0007189, ucf:52263
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0007189
THE IMPACT OF ARTHRITIS ON THE HEALTH-RELATED QUALITY OF LIFE AMONG INDIVIDUALS AT THE UNIVERSITY OF CENTRAL FLORIDA
Title
THE IMPACT OF ARTHRITIS ON THE HEALTH-RELATED QUALITY OF LIFE AMONG INDIVIDUALS AT THE UNIVERSITY OF CENTRAL FLORIDA.
Creator
Garwood, Ryan E., Saleh, Suha, University of Central Florida
Abstract / Description
This purpose of the study is to examine the difference in the health-related quality of life (HRQOL) between individuals who suffer from physician-diagnosed arthritis compared with individuals who do not suffer from physician-diagnosed arthritis in a population of university students, faculty, and staff. The study sampled from a population of students, faculty, and staff at the University of Central Florida. Through the implantation of a cross-sectional ecological design, differences between...
Show moreThis purpose of the study is to examine the difference in the health-related quality of life (HRQOL) between individuals who suffer from physician-diagnosed arthritis compared with individuals who do not suffer from physician-diagnosed arthritis in a population of university students, faculty, and staff. The study sampled from a population of students, faculty, and staff at the University of Central Florida. Through the implantation of a cross-sectional ecological design, differences between the two groups were measured with a survey that measures health-related quality of life, such as the 36-Item Short Form Health Survey (SF-36). The SF-36 questionnaire was distributed to subjects through a campus-wide email system and was administered through Qualtrics, an online survey program. Literature suggests lower SF-36 scores for individuals suffering from arthritis, but is lacking in investigating the effect of arthritis on college-aged students, particularly within the 18-24 age group. The study aims to close this gap in the literature. SPSS software was used to analyze results through tests of association, like ANOVA, which measured differences in the SF-36 scores of subjects with physician-diagnosed arthritis and subjects without physician-diagnosed arthritis. Results showed a significant difference in the HR-QOL scores between individuals with arthritis and individuals without arthritis, as well as age, gender, ethnicity, and the presence of joint pain.
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Date Issued
2017
Identifier
CFH2000189, ucf:46013
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFH2000189