Blood Vessel Study
Condition: Cardiovascular Disease
MeSH terms: Cardiovascular Diseases
Study type: Observational

Summary: 
      Background:

      - The endothelium is the inner lining of blood vessels. The cells in this lining help
      regulate blood flow and immune system function. Problems with endothelial cells can
      contribute to heart disease, high blood pressure, and diabetes. Certain genes or parts of
      genes may be related to problems with endothelial function. Researchers want to study healthy
      adults who have genes that may affect their endothelial function. More information on these
      genes may provide more information on genetic risk for certain diseases.

      Objectives:

      - To study healthy adults who have genetic markers related to endothelial cell problems.

      Eligibility:

        -  Healthy volunteers between 18 and 65 years of age.

        -  Current participants of the Environmental Polymorphisms Registry and have certain genes
           related to endothelial cell problems.

      Design:

        -  Participants will have a single study visit to collect information and samples.

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected.

        -  Participants will have an ultrasound of the artery in the arm and will be given a
           short-acting medication called nitroglycerin to study blood flow and blood pressure.
    

Detailed description: 
      According to the CDC, heart disease is the leading cause of death for both men and women of
      most racial/ethnic groups in the United States, including African Americans, Hispanics, and
      whites. About 610,000 people die of cardiovascular disease (CVD) every year, accounting for 1
      in every 4 deaths (41). Because many known risk factors for heart disease are hereditary,
      understanding the connection between genetics, particularly heritable polymorphisms, and
      cardiovascular disease risk is of great importance. This is a cross-sectional, controlled
      study designed to investigate the association of two single nucleotide polymorphisms (SNPs) -
      a cytochrome P450 (CYP) epoxygenase gene CYP2J2 SNP, CYP2J2 7, and a soluble epoxide
      hydrolase (sEH) gene EPHX2 SNP encoding a K55R variant - with altered endothelial function in
      humans. Healthy adults, aged 18-65 years, who are either carriers of CYP2J2 7 or EPHX2 K55R,
      or who are wild type (WT) with respect to either SNP will be recruited into a total of five
      genotype groups. Potential participants will be identified from the Environmental
      Polymorphisms Registry, mailed an informational letter, contacted by phone and/or email, and
      pre-screened for eligibility. As participants are recruited, demographic characteristics
      (i.e., age, gender, and race/ethnicity) will be compared between the groups, and, if
      necessary, recruitment will be targeted to achieve an approximate match in demographic
      characteristics across the groups. Pre-screened individuals will provide verbal consent to
      refrain from taking certain as needed supplements/medications that could alter endothelial
      function and recreational drugs (such as marijuana, cocaine and amphetamines) prior to the
      study visit, and will be mailed an informed consent form, medical history form, a urine
      collection cup, and pre-visit instructions. Participants will attend a single study visit
      that will take place at the NIEHS Clinical Research Unit. During this visit, written informed
      consent will be obtained, and there will be a final screening and eligibility determination
      including medical history review, assessment of vital signs, physical examination, carbon
      monoxide measurement, pregnancy test (if applicable), and electrocardiogram (ECG). In
      eligible participants, a lipid panel will be performed and endothelial function will be
      assessed non-invasively by brachial artery ultrasound (i.e., flow-mediated dilation) and
      digital peripheral arterial tonometry. Blood and urine (first void) samples will be collected
      for biomarker analyses, which will be conducted in the Zeldin laboratory at NIEHS. The
      primary objective of the study is to determine whether individuals who are homozygous or
      heterozygous for the CYP2J2 7 or EPHX2 K55R SNPs exhibit altered endothelial function
      compared with individuals who are WT for that SNP. As a secondary objective, the impact of
      these two SNPs on inflammatory and CYP epoxygenase pathway biomarkers will be examined.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Genotype data from the EPR will be used to identify potential study participants@@@@@@
      
Keywords: Cardiovascular; P450s; Flow-Mediated Dilation; Brachial Artery Ultrasound; Endothelial Cell Function; Natural History; Healthy Volunteer; HV