Maternal Genetic Variation and Risk of Adverse Pregnancy Outcomes

母亲遗传变异和不良妊娠结果的风险

基本信息

批准号：
7569829
负责人：
Stephanie Engel
金额：
$ 31.94万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-05-15 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7569829
关键词：
Accounting Address Admission activity Angiogenesis Pathway Apoptosis Biological Birth Cell Cycle Child Cohort Studies Control Groups DNA Data Development Disease Enrollment Environmental Risk Factor Etiology Foundations Gene Targeting Genes Genetic Genetic Polymorphism Genetic Variation Genotype Haplotypes Health Human Genetics Hypertension induced by pregnancy Infection Infectious Pregnancy Complications Inflammation Investments Knowledge Laboratories Life Style Link Linkage Disequilibrium Mothers Neonatal Intensive Care Units Outcome Pathway interactions Placentation Play Population Population Study Pregnancy Complications Pregnancy Outcome Premature Birth Research Personnel Risk Role Small for Gestational Age Infant Specimen Ursidae Family Variant Woman angiogenesis base case control cohort cost experience genetic analysis genetic epidemiology interest novel nutrition pregnancy hypertension prospective public health relevance

项目摘要

DESCRIPTION (provided by applicant): Preterm birth, small-for-gestational age (SGA) and pregnancy induced hypertension (PIH) are major pregnancy complications that impact the health of the mother and the child, often resulting in admission to the neonatal intensive care unit following delivery. We propose a highly efficient, intensive pathway-based analysis of genetic variation and preterm delivery, SGA, and PIH that addresses the following specific aims: (1) To investigate the relationship between polymorphisms in the cell-cycle and apoptosis pathways with risk of preterm delivery, SGA, term SGA and pregnancy induced hypertension (PIH); (2) To investigate the relationship between polymorphisms in the angiogenesis pathway with risk of SGA and PIH; (3) To investigate the relationship between polymorphisms in the inflammation pathway with risk of preterm delivery, total and term SGA, and PIH. To address these aims we will be drawing on a well- characterized prospective cohort study of preterm delivery, the Pregnancy, Infection and Nutrition study (PIN), which enrolled over five thousand women over the course of approximately 10 years. In a nested case-control subset of preterm (n=379), term SGA (n=281, an additional 90 are preterm), and PIH cases (n=468) and a random group of controls (n = 936), DNA has already be extracted and is available for genetic analyses. We propose to analyze these DNA specimens using a haplotype-based approach for approximately 93 genes of interest on the Illumina 1536 chip. The priority pathways we have identified bear relevance to the period of placentation, which is a period of development at which these outcomes may be etiologically linked. With additional investment, this cohort could provide the most comprehensive evidence to date linking variants in these pathways of interest with these adverse birth outcomes. PUBLIC HEALTH RELEVANCE: This study promises to generate a markedly enhanced understanding of the genetic epidemiology of preterm, SGA and PIH. This information will provide a foundation for studying other adverse pregnancy outcomes with shared biological mechanisms.

描述（由申请人提供）：早产，小胎龄（SGA）和怀孕诱发的高血压（PIH）是影响母亲和孩子健康的主要妊娠并发症，通常导致入学后接受新生儿重症监护病房。我们提出了对遗传变异和早产，SGA和PIH的高效，基于密集的途径分析，以解决以下具体目的：（1）研究细胞周期和凋亡途径中多态性与早产递送的风险，SGA，SGA和怀孕诱导的高血压（PIH）之间的多态性之间的关系；（2）研究血管生成途径中多态性与SGA和PIH风险之间的关系；（3）研究炎症途径中多态性之间的关系与早产的风险，总和SGA和PIH之间的风险。为了解决这些目标，我们将利用一项针对早产，妊娠，感染和营养研究（PIN）的前瞻性队列研究，该研究在大约10年的时间里招募了五千多名妇女。在早产的嵌套病例对照子集中（n = 379），术语SGA（n = 281，额外的90个是早产）和PIH病例（n = 468）和随机的对照组（n = 936），DNA已被提取，可用于遗传分析。我们建议使用基于单倍型的方法分析这些DNA标本，以在Illumina 1536芯片上大约93个感兴趣的基因。我们确定的优先途径与胎盘时期相关，这是一个发展时期，在该期间，这些结果可能会在病因上联系起来。通过额外的投资，该队列可以提供迄今为止最全面的证据，将这些感兴趣途径中的变体与这些不良的出生结果联系起来。公共卫生相关性：这项研究有望产生对早产，SGA和PIH遗传流行病学的明显增强的理解。该信息将为研究其他不良妊娠结局的基础，并具有共同的生物学机制。