This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The purpose of this research study is to determine if a natural variation in a gene called 'myeloperoxidase' plays a role in the abnormal functioning of blood vessels. It is known that this abnormality of blood vessels affects blood pressure and also leads to heart problems. This is a study of a particular gene, called the myeloperoxidase (MPO) gene, since medical studies have suggested that a certain change in this gene is seen more often in patients with heart disease. This is a study of blood vessel function in people having this variation in the MPO gene compared to a group that does not have the variation. This comparison will be made using a medication called dapsone. Dapsone is known to block the effect of an enzyme called 'myeloperoxidase', produced by the MPO gene. Dapsone is approved by the FDA for treatment of certain skin conditions but is considered investigational for the purpose of this study. Subjects will 1) be between 18 and 45 years old and have no known risk factors for heart disaease or 2) have risk factors for heart disease such as high blood pressure, high cholesterol or have smoked more than 1 pack per day for 20 years and are a) male, aged 45-69 years, or b) postmenopausal women, less than 69 years old. Subjects will be randomly assigned to receive dapsone or placebo.The hypotheses of the study are: 1) The MPO GG genotype is associated with impaired vascular function, and 2) vascular dysfunction in subjects with GG genotype is improved by inhibiting MPO with dapsone therapy.
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