Citation
Relationship Between Nos Gene Methylation And Heart Failure Outcomes

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Title:
Relationship Between Nos Gene Methylation And Heart Failure Outcomes
Series Title:
19th Annual Undergraduate Research Symposium
Creator:
Chen, Davie
Language:
English
Physical Description:
Undetermined

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Subjects / Keywords:
Center for Undergraduate Research
Center for Undergraduate Research
Genre:
Conference papers and proceedings
Poster

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Abstract:
The nitric oxide synthase (NOS) genes play a key role in synthesis of nitric oxide, an important signaling molecule in the cardiovascular system. DNA methylation regulates gene expression and its regulation of NOS genes could impact heart failure (HF) outcomes. The aim of this project was to explore the relationship between DNA methylation and clinical outcomes in HF patients. Clinical data from the University of Illinois at Chicago Heart Failure Database, along with DNA methylation data obtained from Illumina Human Methylation 450K array were used in various survival analyses. The NCBI database and UCSC Genome Browser were used to determine the loci of the NOS1, NOS2, and NOS3 genes, with an additional 500kb on each end. In both the NOS1 and NOS2 gene regions, there does not appear to be an association between mean methylation and HF outcome, with neither having an adjusted p-value less than 0.05. However, the NOS3 region seems to show a possible trend in hospitalization outcomes (hazard ratio: 0.0001406 P=0.09) and death/hospitalization combined outcomes (hazard ratio: 0.0001743 P=0.08). Our data suggest that regulation of NOS3 expression by DNA methylation may play a role in adverse cardiovascular outcomes in HF patients, but further validation is needed. ( en )
General Note:
Research authors: Davie Chen, Julio Duarte - University of Florida
General Note:
University Scholars Program
General Note:
Faculty Mentor: The nitric oxide synthase (NOS) genes play a key role in synthesis of nitric oxide, an important signaling molecule in the cardiovascular system. DNA methylation regulates gene expression and its regulation of NOS genes could impact heart failure (HF) outcomes. The aim of this project was to explore the relationship between DNA methylation and clinical outcomes in HF patients. Clinical data from the University of Illinois at Chicago Heart Failure Database, along with DNA methylation data obtained from Illumina Human Methylation 450K array were used in various survival analyses. The NCBI database and UCSC Genome Browser were used to determine the loci of the NOS1, NOS2, and NOS3 genes, with an additional 500kb on each end. In both the NOS1 and NOS2 gene regions, there does not appear to be an association between mean methylation and HF outcome, with neither having an adjusted p-value less than 0.05. However, the NOS3 region seems to show a possible trend in hospitalization outcomes (hazard ratio: 0.0001406 P=0.09) and death/hospitalization combined outcomes (hazard ratio: 0.0001743 P=0.08). Our data suggest that regulation of NOS3 expression by DNA methylation may play a role in adverse cardiovascular outcomes in HF patients, but further validation is needed. - Center for Undergraduate Research, University Scholars Program

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University of Florida
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Copyright Davie Chen. Permission granted to University of Florida to digitize and display this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.

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Relationship Between NOS Gene Methylation and Heart Failure Outcomes Davie Chen and Julio Duarte Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, FL Methods Conclusions Introduction Results o Heart disease is a leading cause of death worldwide, with heart failure patients having some of the worst outcomes. o DNA methylation, a transcription regulation mechanism involving the addition of a methyl group without changing the base sequence, might offer insight on contributors to severe outcomes in those patients. o Our area of interest is the nitric oxide synthase (NOS) genes, responsible for the synthases that produce nitric oxide, an important signaling molecule. o The goal of this project was to identify associations between DNA methylation patterns and risk of severe cardiovascular outcomes in patients with heart failure. o Clinical data was obtained from the University of Illinois at Chicago Heart Failure Database, and all patients provided informed written consent before being included in the database. o DNA methylation data (in M values) were obtained using the Illumina Human Methylation 450K array. o Cox proportional hazard tests were performed to assess the risk of death, hospitalization, and total combined risk of both. o Three analyses were performed, one on global methylation, one on individual NOS gene mean methylations, and one on the methylation of CpG sites within the NOS region. o Global methylation shows a possible protective trend towards mortality risk ; however, the number of deaths in the sample was very low only 9 out the 118 patients o Mean methylation within the NOS 3 gene region seems to show a protective trend towards combined mortality and hospitalization risk as well as hospitalization risk alone o Methylation at the cg 00963113 CpG site seems to show a trend towards increased mortality risk, the site itself is part of a transmembrane protein of unknown function o Methylation at the cg 13666659 CpG seems to show a trend towards decreased hospitalization risk o The methylation data in our analyses was obtained from blood cells, a future analysis with methylation data from cardiomyocytes could offer more insight o The roles of genes that the CpG sites are found in could also be explored o Increased global methylation trended towards a decreased mortality risk (HR: 3.402e 135). o In NOS gene region, increased mean methylation in the NOS3 region trended with a decrease in combined hospitalization and mortality risk (HR:0.0001743) as well as the hospitalization risk alone (HR: 0.0001406) o Two probes, cg00963113 (Gene: TMEM176B) and cg13666659 (Gene: NLK), were highly significantly associated (p Figure 1. Associations between global methylation and clinical outcomes in HF patients Figure 2. Associations between mean NOS methylation and clinical outcomes in HF patients Figure 3. Associations between individual methylation sites within NOS gene regions and clinical outcomes in HF patients