Hypertension is a major public health problem, affecting nearly one-third of adults over age 20 in the United States. While the prevalence of hypertension is <10% in adults between 20 - 34 years of age, the development of hypertension is a long-term process, and blood pressure levels during childhood and adolescence are correlated with levels at later ages. Understanding the factors involved in regulating blood pressure in childhood, through adolescence, and into adulthood will be valuable both in understanding the pathology of hypertension and in targeting preventive measures most effectively. Genetic factors are known to play a significant role in regulating blood pressure, and even though most genes contributing to interindividual variation in risk of hypertension will have relatively small effects on risk for any given individual, their aggregate effects contribute significantly to risk of hypertension in the overall population. Due to the difficulty of studying large numbers of individuals over long periods of time, relatively little is known about the effects of genetic variants on the changes in blood pressure which occur with age. The Bogalusa Heart Study (BHS), which began as a study of cardiovascular disease (CVD) risk factors in children but evolved to cover the development of CVD risk factors from childhood into early middle age, offers an unparalleled resource for investigating the genetic factors influencing within-individual changes over time in blood pressure and other quantitative CVD risk factors, such as serum lipids. In the proposed research, we will measure an average of 37 single-nucleotide polymorphisms in each of 75 genes either known or strongly suspected to affect interindividual variation in blood pressure and risk of hypertension, in a sample of 1564 individuals who were examined in the BHS on at least 3 separate occasions over a period of up to 23 years, and who consented to participate in studies of genetic factors influencing CVD risk. Subjects were between 4 and 38 years of age when examined. Multilevel regression will be used to measure the effect of these variants on longitudinal blood pressure profiles and to determine whether some genes have age-dependent effects on blood pressure. The proposed research promises to extend greatly our knowledge of the genetic factors affecting blood pressure levels over a substantial portion of an individual's lifetime. In addition, because many genes which affect blood pressure have pleiotropic effects on other CVD risk factors, such as adiposity and serum triglycerides, the proposed research will also provide opportunities for investigating genetic factors influencing the development of the metabolic syndrome marked by hypertension, insulin resistance, obesity, and dyslipidemia.
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