Influence of Nitric Oxide Synthase Gene on
Blood Pressure & Subclinical Cardiovascular System Changes An American Heart Association supported genetic epidemiologic study to examine the effect of the endothelial nitric oxide synthase gene on serial changes of blood pressure and the anatomic alterations of the cardiovascular system. Investigators
Wei Chen, MD, PhD, Principal Investigator
Gerald S. Berenson, MD, Co-Investigator
Sathanur R. Srinivasan, PhD, Co-Investigator
Eric Boerwinkle, PhD, Co-Investigator Funding Agent
American Heart AssociationParticipating Institutes
Tulane University Health Sciences Center
University of Texas Health Science Center at Houston Description
Endothelial nitric oxide plays an important role in the pathophysiology of hypertension and coronary heart disease. However, little is known about the influence of endothelial nitric oxide synthase (eNOS) gene polymorphisms on longitudinal effects on blood pressure and subclinical changes of the cardiovascular system in youth. The specific aims of the proposed study are to examine the effects of polymorphic variations in the eNOS gene and its interaction with insulin resistance on 1) serial changes of blood pressure from childhood to adulthood, and 2) the anatomic alterations of the cardiovascular system noted by intima-media thickness (IMT) of carotid arteries and left ventricle mass (LVM) in adulthood. The Bogalusa Heart Study, a 27-year long-term epidemiologic study of cardiovascular risk factors from birth through 39 years of age, offers an unparalleled database of achieving these aims. In the proposed study, 1,015 unrelated subjects, who were screened at least 3 times between 1973 and 1996, will be typed for five polymorphic markers at the eNOS gene locus. Data on carotid IMT and cardiac LVM are available for a subsample of adults (n=507). The MIXED model with REPEATED MEASURES method, tracking analysis and variance component model will be used to examine the effects of the eNOS gene and its interaction with insulin resistance on longitudinal profiles of blood pressure in terms of both levels and within-subject variations over time. Generalized linear model will be used to characterize the relationship of the eNOS gene, blood pressure and insulin resistance to IMT and LVM. The proposed study will extend our knowledge of genetic and biologic basis of the early natural history of hypertension and subclinical structural changes of the cardiovascular system. |
