Genetic Modulation on the Relationship of Low Birth Weight to Metabolic Syndrome

低出生体重与代谢综合征关系的基因调控

• 批准号: 7886218
• 负责人: WEI CHEN
• 金额: $ 7.45万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-16 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7886218
• 关键词: Adult; African American; Birth; Birth Certificates; Birth Weight; Blood Glucose; Blood Pressure; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Childhood; Cholesterol; Cohort Studies; Communities; Complex; Cross-Sectional Studies; Data; Fetal Growth Retardation; Genes; Genetic; Genotype; Growth; Haplotypes; Heart; Heart Diseases; Hypertension; Individual; Insulin Resistance; Lead; Lipoproteins; Longitudinal Studies; Low Birth Weight Infant; Measurement; Measures; Metabolic syndrome; Modeling; Natural History; Nature; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Phenotype; Prenatal care; Research; Risk Factors; Single Nucleotide Polymorphism; Statistical Methods; Testing; Time; base; cardiovascular risk factor; cohort; diabetes risk; fetal; gene interaction; genetic analysis; genetic association; improved; longitudinal database; prevent; public health relevance; trend

DESCRIPTION (provided by applicant): Low birth weight, an indicator of intrauterine growth restriction, has been demonstrated to be associated with adult cardiovascular (C-V) disease, type 2 diabetes and metabolic syndrome components, including body fatness, insulin resistance measures, blood pressure, and lipoproteins. The interrelationship of low birth weight to multiple components of the metabolic syndrome as a complex entity and the underlying genetic factors can be elucidated further using an advanced sophisticated statistical method like path analysis. The Specific Aims of the proposed research are 1) to examine the impact of low birth weight on metabolic syndrome components by using a path analysis model, longitudinally and cross-sectionally by growth periods, in black versus white individuals, and 2) to investigate the modifying effects of relevant candidate genes on the relationship of low birth weight to longitudinal trends of metabolic syndrome components from childhood to adulthood. These specific aims will be examined using existing phenotypes and candidate gene genotype data available in the Bogalusa Heart Study, a long-term biracial (65% white, 35% black) community-based study of the Natural History of C-V Disease beginning in childhood, since 1973. Study Cohort I for cross-sectional analyses by growth periods consists of 6,051 individuals who have State birth certificate information and metabolic syndrome components; Cohort II for longitudinal analyses consists of 2,775 individuals who have data on birth weight and serial measurements of metabolic syndrome components measured at least 2 times each in childhood and in adulthood during 1973-2008, with 16,276 observations; Cohort III (n=1,447, 990 whites, 457 blacks) for genetic analyses is a subset of Cohort II with candidate gene genotype data available. Single nucleotide polymorphisms (SNPs, n=618) in 21 candidate genes related to both birth weight and metabolic syndrome will be analyzed as individual SNPs, haplotypes and gene-gene interactions. Path analyses will be performed cross-sectionally and longitudinally to examine the relationship of birth weight to the metabolic syndrome components by haplotype groups. The modulating effect of the candidate genes will be tested in terms of significant differences in the path analysis parameters between haplotype groups. The genetic loci identified in the proposed research will provide a basis for further research on the pleiotropic effects and additive effects of multigenes, and more dense sequencing in significant candidate genes in subjects who have a low birth weight and extremes values of the metabolic syndrome variables. This has important implications for improving prenatal care and developing strategies beginning early to prevent adult C-V disease. PUBLIC HEALTH RELEVANCE: Low birth weight is an indicator of baby growth restriction before birth, and associated with adult heart disease, diabetes and risk factors such as obesity, high blood pressure, high cholesterol and high blood sugar. The findings from this research has important implications for improving prenatal care and developing strategies beginning early to prevent adult heart disease.

描述（由申请人提供）：已经证明，低出生体重是宫内生长限制的指标，已证明与成人心血管疾病（C-V）疾病，2型糖尿病和代谢综合征成分有关，包括身体脂肪，包括体内脂肪，胰岛素抵抗，血压，血压，血压和脂蛋白。可以使用先进的复杂统计方法（如路径分析）进一步阐明，可以将低出生权与代谢综合征的多个组成部分的相互关系和基础遗传因素的相互关系进一步阐明。拟议的研究的具体目的是1）通过使用路径分析模型，通过增长期，黑人与白人个体来检查低出生体重对代谢综合征成分的影响，以研究相关候选基因对纵向组成型的较低生物趋势的关系的修改影响。将使用现有的表型和候选基因基因型数据来检查这些具体目标，这是Bogalusa心脏研究中的一项长期混血儿（65％白人，35％，黑色，黑色为35％），自1973年以来开始对C-V疾病的自然历史研究。自1973年以来，C-V疾病的自然历史。研究同龄人由6 ,,05的人组成的跨分类时间组成的研究群体由跨分类时间组成，这些人的综合综合有综合综合。纵向分析的队列II由2,775个人组成，这些个体具有有关出生体重的数据和代谢综合征成分的序列测量数据，这些成分在童年时期和1973年至2008年的成年期至少测量了2次，有16,276的观察结果；遗传分析的队列III（n = 1,447，990白色，457个黑人）是与可用的候选基因基因型数据的同类II子集。与出生体重和代谢综合征相关的21个候选基因中的单核苷酸多态性（SNP，n = 618）将被分析为单个SNP，单倍型和基因基因相互作用。路径分析将在横截面和纵向上进行，以检查单倍型组的出生体重与代谢综合征成分的关系。候选基因的调节作用将根据单倍型组之间的路径分析参数的显着差异进行测试。在拟议的研究中鉴定的遗传基因座将为多烯的多效效应和添加剂的进一步研究提供基础，并在具有较低出生体重和代谢综合征变量的极端值的受试者中进行多基因的累加作用，并在重要的候选基因中进行更密集的测序。这对于改善产前护理和制定策略的重要意义，从早期开始，以防止成人C-V疾病。 公共卫生相关性：低出生体重是出生前婴儿生长限制的指标，与成人心脏病，糖尿病和危险因素有关，例如肥胖，高血压，高胆固醇和高血糖。这项研究的发现对改善产前护理和制定策略的重要意义，以防止成人 心脏病。