The COX-2 Gene and the Immune System

Overview

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.

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.