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

NCT01143519 | Completed

• 2 other identifiers: 10013410-E-0134
• Study Type: observational
• Target: 178
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV-1 Seropositive; Inflammation; Cancer; Cardiomyopathy

Keywords

Gene Expression; Apoptosis; Lymphocytes; Environmental Factors; Single Nucleotide Polymorphism; Natural History; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• p53 target gene expression

  The primary endpoint of this study is p53 target gene expression measured by RTPCR for the following five SNPs: p53 rs1042522, MDM2 rs2279744, FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952.

  analysis on blood drawn at visit

Secondary Outcomes (1)

• p53 promoter occupancy

  analysis on blood drawn at visit

Study Arms (5)

FLT1 C-677T

SNP

MDM2 rs2279744

SNP

p53 rs1042522

SNP

RMM1 rs1465952

SNP

TLR8 rs3761624

SNP

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants at the age of 18 years and older carrying one of the following SNPs: p53 rs1042522, MDM2 rs2279744, FLT1 C-677T, TLR8 rs3761624 and RMM1 rs1465952 in the p53 promoter region or in p53 target gene RE regions and wild-type controls will be identified from the Environmental Polymorphism Registry (EPR).

You may qualify if:

• Male or female 18 years of age or older
• Participants must be able to understand and provide written informed consent to participate in the study
• Participants must be able to travel to the CRU
• Nonpregnant
• Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. If the individual has a chronic condition such as diabetes or high blood pressure, healthy also means that they are being treated and the condition is under control).
• Participants with health outcomes identified by genotype-phenotype association studies.
• HIV-1 seropositive under medicament treatment (for HIV P53 and TLR8 groups only) (checked every 6 months at visit)

You may not qualify if:

• Use of immunosuppressants or other immune-modifying drugs \[e.g., Rituxan, Humira, Enbrel, Cyclosporin (Neoral, Sandimmune, and SangCya), Azathioprine (Imuran)\], Monoclonal antibodies \[e.g., infliximab (Remicade)\] (for healthy controls only)
• Chronic use of systemic, inhaled steroids
• Current or use of prescription strength topical corticosteroids within the last 7days
• History of cancer, including skin cancer (for healthy controls only)
• History of chemotherapy or radiation treatment (for healthy controls only)
• Confirmed or suspected immunosuppressive or immunodeficient condition (for healthy controls only)
• Hepatitis B/C-positive status (checked every 6 months at visit)
• Body weight \< 50 kg (\<110 lbs)
• If blood donation exceeds 200ml:
• Hematocrit \<34% for women or \<36% for men, or \>56% for either gender
• Temperature \> 37.6 C; blood pressure \< 90/50 mm Hg or blood pressure \>160/100 mm Hg; pulse rate \< 50 or \> 100 beats/minute
• Blood or plasma donation that will cause the participant to exceed 550ml of blood in the last 8 weeks
• HIV1 donors with opportunistic infections:
• Candidiasis of bronchi, trachea, esophagus, or lungs
• Invasive cervical cancer

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (1)

NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, United States

Location

Related Publications (3)

• Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, Bargonetti J, Bartel F, Taubert H, Wuerl P, Onel K, Yip L, Hwang SJ, Strong LC, Lozano G, Levine AJ. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004 Nov 24;119(5):591-602. doi: 10.1016/j.cell.2004.11.022.

  PMID: 15550242 BACKGROUND

• Menendez D, Inga A, Resnick MA. The expanding universe of p53 targets. Nat Rev Cancer. 2009 Oct;9(10):724-37. doi: 10.1038/nrc2730.

  PMID: 19776742 BACKGROUND

• Murphy ME. Polymorphic variants in the p53 pathway. Cell Death Differ. 2006 Jun;13(6):916-20. doi: 10.1038/sj.cdd.4401907. No abstract available.

  PMID: 16557270 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Inflammation; Neoplasms; Cardiomyopathies

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Study Officials

• Daniel Menendez Rendon, Ph.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2010
• First Posted: June 14, 2010
• Study Start: May 21, 2012
• Last Updated: April 17, 2026

Record last verified: 2025-05-02

Locations

US (1)