We propose to determine if the mechanism for the development of pulmonary hypertension (PH) in patients who have taken the anorectic dexfenfluramine or fenfluramine is due to the reduced rate of metabolism through recessively inherited polymorphism of the cytochrome P450 2D6 gene. Patients with PH with a history of anorectic treatment will be compared with sporadic PH patients, normal subjects and controls of same age and sex but with congestive cardiomyopathy. The phenotypes for PH will be characterized by physiological measurements and measurements of endothelial and platelet products known to be altered in the disease. The genotypes for different alleles of the CYP2D6 gene will identify those who are poor metabolizers. Biochemical markers of endothelial dysfunction, i.e. urinary metabolites of prostacyclin, thromboxane and nitric oxide, will be measured as well as circulating and platelet storage levels of amines and endothelin-1.
|Demoncheaux, Eric A G; Higenbottam, Tim W; Kiely, David G et al. (2005) Decreased whole body endogenous nitric oxide production in patients with primary pulmonary hypertension. J Vasc Res 42:133-6|