The COX-2 Gene and the Immune System
Condition: Allergic Inflammation; Asthma
MeSH terms: Inflammation
Study type: Observational

Summary: 
      Background:

      - The immune system contains several different types of cells in the blood and other parts of
      the body. The body can fight infections well with the right balance of these cell types. The
      wrong balance of cell types may cause diseases, such as allergies or asthma. The COX-2 gene
      may help decide the balance of cell types that the body makes as part of the immune system.
      It may also play a role in certain immune system diseases. Researchers want to see how COX-2
      affects the cells in the immune system.

      Objectives:

      - To study how the COX-2 gene works in the body s immune system.

      Eligibility:

      - Individuals 18 years of age and above who are part of the Environmental Polymorphisms
      Registry.

      Design:

        -  Participants will have one study visit at the National Institutes of Health. They will
           collect a urine sample at home on the morning of the study visit.

        -  Participants will have a physical exam and medical history. They will provide a blood
           sample. They will also give researchers the urine sample they collected that morning.

        -  No treatment will be provided as part of this study.
    

Detailed description: 
      This is a cross-sectional, controlled study designed to investigate the association of single
      nucleotide polymorphisms (SNPs) in the cyclooxygenase-2 (COX2) gene, also called
      prostaglandin endoperoxidase synthase 2 (PTGS2), on T-cell differentiation and function.
      Specifically, the impact of the promoter-region SNP 765G>C (rs20417) and the 3 untranslated
      region (UTR) SNP 8473T>C (rs5275) on T helper cell (Th) 2, Th9, and Th17 differentiation and
      function will be examined. Non-Hispanic, White or Black/African American, non-pregnant
      adults, aged 18-65 years, who are wild type (WT), with respect to both the 765G>C and 8473T>C
      SNPs, WT with respect to 765G>C and homozygous for 8473T>C, and homozygous for both 765G>C
      and 8473T>C will be recruited into a total of three genotype groups. Potential participants
      will be identified from the Environmental Polymorphisms Registry, contacted by recruitment
      letter and pre-screened for eligibility. Pre-screened individuals will provide verbal consent
      to withhold certadata analysis, a urine collection cup, and pre-visit instructions.
      Participants will attend a single study visit that will take place at the National Institute
      of Environmental Health Sciences (NIEHS) Clinical Research Unit (CRU). During this visit,
      written informed consent will be obtained, and there will be a final screening and
      eligibility determination, medical history review, vital signs, physical examination and
      blood and urine samples will be collected. From peripheral blood, lymphocyte subsets,
      prostaglandin levels, and cytokine levels will be determined; stable prostaglandin
      metabolites, creatinine, total protein and albumin will be measured in urine. Lymphocytes
      will be isolated from peripheral blood for ex vivo analyses. Demographic characteristics
      (i.e., age) will be compared between the groups, and when possible, recruitment will be
      targeted to achieve an approximate match of race and gender across the groups. The primary
      objective of the study is to determine whether the 765G>C or 8473T>C SNPs exhibit altered
      Th2, Th9 and Th17 cell differentiation by examining lymphocyte subsets in vivo. The study
      will also examine the impact of these two SNPs on circulating Th2/Th9/Th17 cytokine levels
      and prostaglandins in vivo, on differentiation of naive CD4+T-cells to Th cell subsets in
      vitro, and on lymphocyte production of cytokines and prostaglandins in vitro.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        individuals who are homozygous for either the major or minor variant of both SNPs@@@
      
Keywords: Lymphocyte; Prostaglandin Endoperoxidase Synthase 2; COX-2; Natural History