Genetic Epidemiology of Change in CVD Risk Factors

CVD危险因素变化的遗传流行病学

基本信息

批准号：
7882675
负责人：
DAVID MICHAEL HALLMAN
金额：
$ 54.43万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-29 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7882675
关键词：
Adolescence Adolescent Adult Affect Age Age-Years Aging-Related Process Blood Pressure Candidate Disease Gene Cardiovascular Diseases Child Childhood Communities Consent Data Development Diet Dyslipidemias Exercise Gene Frequency Genes Genetic Genetic Polymorphism Genetic Variation Heart High Density Lipoprotein Cholesterol Hypertension Hypertriglyceridemia Hypotension Individual Insulin Resistance Knowledge Lipids Measurement Measures Metabolic syndrome Non-Insulin-Dependent Diabetes Mellitus Obesity Participant Pathogenesis Pathology Pattern Pharmaceutical Preparations Pharmacogenetics Phenotype Play Population Prevalence Preventive Process Public Health Regimen Research Research Personnel Resources Risk Risk Factors Role Sampling Serum Single Nucleotide Polymorphism Smoking Syndrome Time Triglycerides United States Variant age related base blood pressure regulation cardiovascular disorder risk genetic epidemiology genetic variant genome wide association study high risk hypertension control impaired glucose tolerance lifestyle factors middle age novel strategies programs trait

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：高血压是一个主要的公共卫生问题，影响着美国近三分之一的 20 岁以上成年人。虽然20-34岁成人中高血压的患病率<10%，但高血压的发展是一个长期过程，儿童和青少年时期的血压水平与以后年龄的水平相关。了解儿童期、青春期和成年期血压调节所涉及的因素对于了解高血压的病理学和最有效地采取预防措施都是有价值的。众所周知，遗传因素在调节血压方面发挥着重要作用，尽管大多数导致高血压风险个体差异的基因对任何特定个体的风险影响相对较小，但它们的总体效应对高血压风险有显着影响。总人口。由于长期研究大量个体存在困难，人们对遗传变异对随年龄增长的血压变化的影响知之甚少。 Bogalusa 心脏研究 (BHS) 最初是一项针对儿童心血管疾病 (CVD) 危险因素的研究，后来发展到涵盖从儿童期到中年早期 CVD 危险因素的发展，为研究影响心血管疾病 (CVD) 的遗传因素提供了无与伦比的资源。个体内部血压和其他定量 CVD 危险因素（例如血脂）随时间的变化。在拟议的研究中，我们将在 BHS 检查的 1564 名个体样本中，测量已知或强烈怀疑会影响个体间血压差异和高血压风险的 75 个基因中的每一个基因中的平均 37 个单核苷酸多态性。在长达 23 年的时间里至少有 3 次不同的经历，并且同意参加影响 CVD 风险的遗传因素的研究。检查时受试者年龄在 4 岁至 38 岁之间。多级回归将用于测量这些变异对纵向血压曲线的影响，并确定某些基因是否对血压具有年龄依赖性影响。拟议的研究有望极大地扩展我们对影响个体一生大部分时间血压水平的遗传因素的认识。此外，由于许多影响血压的基因对其他CVD危险因素（例如肥胖和血清甘油三酯）具有多效性，因此拟议的研究还将为研究影响以高血压、胰岛素抵抗为标志的代谢综合征发展的遗传因素提供机会。、肥胖和血脂异常。