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.
Description: -Change in digital pulsatile pressure-Endothelium-independent vasodilation-Change in brachial artery blood flow velocity -Serum levels of inflammatory markers -Serum and urine levels of cytochrome P450 epoxygenase pathway biomarkers
Measure: -Change in digital pulsatile pressure-Endothelium-independent vasodilation-Change in brachial artery blood flow velocity -Serum levels of inflammatory markers -Serum and urine levels of cytochrome P450 epoxygenase pathway biomarkers@... Time: analysisDescription: -Change in digital pulsatile pressure-Endothelium-independent vasodilation-Change in brachial artery blood flow velocity -Serum levels of inflammatory markers -Serum and urine levels of cytochrome P450 epoxygenase pathway biomarkers
Measure: -Change in digital pulsatile pressure-Endothelium-independent vasodilation-Change in brachial artery blood flow velocity -Serum levels of inflammatory markers -Serum and urine levels of cytochrome P450 epoxygenase pathway biomarkers@... Time: analysisCohort
There is one SNP
The Role of the Functionally Relevant Single Nucleotide Polymorphisms CYP2J2 -50G>T (CYP2J2 7) and EPHX2 9846A>G (EPHX2 K55R) in Human Endothelial Function. --- K55R ---
- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R ---
- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R ---
- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R ---
- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R --- --- K55R ---
- INCLUSION CRITERIA: - Participant of the Environmental Polymorphisms Registry and current contact information available - Genotype information available for relevant CYP2J2 and EPHX2 polymorphisms, which indicates: - WT for EPHX2 K55R and WT for CYP2J2 7 - WT for EPHX2 K55R and heterozygous for CYP2J2 7 - WT for EPHX2 K55R and homozygous for CYP2J2 7 - WT for CYP2J2 7 and heterozygous for EPHX2 K55R (N=30) - WT for CYP2J2 7 and homozygous for EPHX2 K55R (N=30) - Age 18-70 years - Willing and able to provide informed consent - Able to comply with all protocol procedures EXCLUSION CRITERIA: - Currently pregnant or breast feeding - Hospitalized for a cardiovascular disease or stroke event within the previous 3 months - Current use of long-acting nitrates (e.g., isosorbide mononitrate, isosorbide dinitrate) - Current use of medications taken for hypertension. --- K55R --- --- K55R --- --- K55R --- --- K55R --- --- K55R ---
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. --- K55R ---
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. --- K55R ---
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. --- K55R ---