Study of the Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage
|First Received Date ICMJE||June 11, 2010|
|Last Updated Date||February 4, 2014|
|Start Date ICMJE||May 2010|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT01143519 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of the Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage|
|Official Title ICMJE||Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage|
- Research has shown that certain proteins in cells may be linked to higher risks of developing inflammations, tumors, and other medical problems. By examining how the blood cells of healthy volunteers respond to environmental exposures, researchers hope to better understand the relationship of genes, environmental factors, and human diseases.
- To examine how specific genes and proteins in blood cells respond to environmental exposures.
- Healthy volunteers between 18 and 45 years of age.
This research study will investigate the role of SNPs in p53 and p53 response elements on the inflammatory response to DNA damage. A total of 210 healthy participants aged 18 years and older carrying one of the seven SNPs of interest and wild-type controls will be identified and recruited from the Environmental Polymorphism Registry (EPR). The EPR is a long-term project to collect and store up to 15,000 DNA samples for use in research studies from individuals in the greater North Carolina Triangle Region.
This observational gene association study will recruit participants on the basis of genotype and then observe the phenotype of each participant. The SNPs of interest are p53, as well as four of its downstream target genes including FLT1, MDM2, TLR8 and RRM1. A maximum of 150 mLs of blood will be obtained from each participant during one visit lasting approximately one hour. Cells from the donated blood samples will be examined for their response to exposed environmental stress ex vivo.
The primary objective is to determine the association between seven SNPs and p53 target gene expression after exposure to Nutlin or doxorubicin (chemotherapeutic agents) with outcome measured by RT-PCR. The seven SNPs are p53 rs1042522, p53 rs1800371, MDM2 rs2279744, MDM2 rs769412, FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952. The secondary objectives are to: (1) to determine the p53 promoter occupancy measured by ChIP analysis for the following SNPs: FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952; (2) to measure apoptosis by Annexin V-PI assay for SNPs p53 rs1042522 and p53 rs1800371; (3) to examine the cell cycle profile analysis (FACS) by cytofluorometry for SNPs p53 rs1042522 and p53 rs1800371; and (4) to determine DNA repair using Pulse Field Electrophoresis Gel (TAFE gels) for the following SNPs p53 rs1042522 and p53 rs1800371.
We hope the results of this study lead to discovery of important information regarding the role of SNPs located in p53 and p53 response elements in human disease, potentially identifying new targets for future studies.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Intervention ICMJE||Not Provided|
|Study Group/Cohort (s)||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||420|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||Yes|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT01143519|
|Other Study ID Numbers ICMJE||100134, 10-E-0134|
|Has Data Monitoring Committee||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Environmental Health Sciences (NIEHS)|
|Collaborators ICMJE||Not Provided|
|Information Provided By||National Institutes of Health Clinical Center (CC)|
|Verification Date||January 2014|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP