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Study of the Effect of SNPs in p53 and p53 Response Elements on the Inflammatory Response to DNA Damage

2014-08-27 03:12:55 | BioPortfolio

Summary

Background:

- 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.

Objectives:

- To examine how specific genes and proteins in blood cells respond to environmental exposures.

Eligibility:

- Healthy volunteers between 18 and 45 years of age.

Design:

- The study will involve one visit of 45 to 60 minutes.

- Participants will be screened with a brief physical examination and finger stick to determine if they are eligible to donate blood for the study, and will complete a questionnaire about any medications or other drugs (e.g., cigarettes) they may be taking.

- Participants will provide a blood sample for research purposes.

Description

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 volunteers aged 18 - 45 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 Design

N/A

Conditions

Inflammation

Location

NIEHS Clinical Research Unit (CRU)
Research Triangle Park
North Carolina
United States

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:55-0400

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