GENE TARGETS FOR IVH

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 大量研究证实，3-4级脑室出血(IVH)是极低出生体重(VLBW)新生儿不良结局的重要原因。IVH，或发育中脑组织生发基质组织的出血，被认为是继发于未成熟生发基质微血管的脑血流变化和继发性脑室周围静脉梗塞。超过12%的极低出生体重儿经历GR。3-4名IVH患者，其中四分之三发展为智力低下、脑瘫和/或癫痫。 根据美国人口普查局、NICHD新生儿网络和疾控中心的数据，有超过3600例新的智力低下病例可归因于GR。在美国，每年有3-4个IVH，这些孩子一生的护理费用超过36亿美元。早产代表着大脑发育的独特环境；许多因素，如炎症、低血压 导致IVH的低氧血症已经被确定。Gr.然而，在过去的十年里，3-4 IVH没有改变。直到最近，关于遗传因素是否在GR的发病机制中发挥作用的信息有限。3~4例IVH。然而，新的数据有力地表明，极低出生体重双胞胎的IVH易感性为家族遗传，而且有几项研究已经 探讨血栓形成、炎症和血管基因在GR发生中的作用。3~4例IVH。我们假设对于极低出生体重的婴儿，Gr。3-4IVH既有环境因素，也有遗传因素。遗传因素是尚未确定的基因的等位基因和单倍型，使极低出生体重儿易患GR。3~4例IVH。很可能许多人都是 炎症、血管、氧化和/或凝血途径。为了实现这些目标，这项随机、多中心的研究将收集1000名出生体重在500-1250克之间的Gr新生儿的DNA。正常早产儿3-4例IVH和1000例配对对照早产儿 做了头颅超音波检查，没有脑室出血的证据。遗传分析将包括分布在整个基因组中的50万个标记的全基因组关联研究，以及针对编码为血管、炎症、氧化和/或凝血途径的已知蛋白质的基因的候选途径基因研究。以确定环境因素对GR的贡献。3-4将收集IVH、产前、围产期和新生儿数据；使用 多变量分析，将评估遗传和环境因素对IVH易感性的相对贡献。 这是一项由美国国立卫生研究院资助的随机多中心试验，贝勒医学院是参与试验的14个机构之一。研究的婴儿总数将为1000名患有3级或4级IVH的婴儿和1000名匹配的对照组婴儿。注册将在研究的前四年进行。我们的网站计划在四年的授权期内招募总共248名婴儿(124名患有3级或4级IVH的婴儿和124名匹配的对照婴儿)。 1.对早产儿来说，IVH是环境和遗传因素共同作用的结果。 2.遗传因素是尚未确定的基因的等位基因和单倍型，这些基因使出生在500-1250克的极低出生体重儿容易发生IVH。 3.这些基因中有许多是血管、炎症、氧化和/或凝血途径的一部分。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Numerous studies have identified Grades 3-4 intraventricular hemorrhage (IVH) as a significant cause of adverse outcome for very low birthweight (VLBW) neonates. IVH, or hemorrhage into the germinal matrix tissues of the developing brain, is believed to be secondary to changes in cerebral blood flow to the immature germinal matrix microvasculature and secondary periventricular venous infarction. Over 12% of all VLBW infants experience Gr. 3-4 IVH, and three quarters of these develop mental retardation, cerebral palsy and/or seizures. Based on data from the U.S. Census Bureau, the NICHD Neonatal Network and the CDC, there are over 3600 new cases of mental retardation attributable to Gr. 3-4 IVH in the U.S. each year, and the lifetime care costs for these children exceed 3.6 billion dollars. Preterm birth represents a unique environment for the developing brain; many factors such as inflammation, hypotension and hypoxemia that contribute to IVH have been identified. The incidence of Gr. 3-4 IVH has not changed, however, over the past ten years. Until recently, there has been limited information on whether genetic factors play a role in the pathogenesis of Gr. 3-4 IVH. New data, however, strongly suggest familial susceptibility for IVH in VLBW twins, and several studies have investigated the role of thrombophilia, inflammatory and vascular genes in the genesis of Gr. 3-4 IVH. We hypothesize that for VLBW infants, Gr. 3-4 IVH is attributable to both environmental and genetic factors. The genetic factors are alleles and haplotypes of as yet unidentified genes that render VLBW infants susceptible to Gr. 3-4 IVH. It is likely that many are part of inflammatory, vascular, oxidative and/or coagulation pathways. To accomplish these aims, this randomized, multi-center study, in aggregate, will collect DNA from 1000 neonates of 500-1250g birthweight with Gr. 3-4 IVH and 1000 matched control preterm infants with normal cranial ultrasounds and no evidence for IVH. The genetic analyses will include a whole genome association study of 500,000 markers distributed throughout the genome and candidate pathway gene studies targeting genes that encode proteins known to subserve vascular, inflammatory, oxidative and/or coagulation pathways. In order to determine the contribution of environmental factors to Gr. 3-4 IVH, pre-, peri- and neo-natal data will be collected; using multivariate analyses, the relative contribution of genetic and environmental factors to the susceptibility to IVH will be assessed. This is an NIH funded, randomized multi-center trial, of which Baylor College of Medicine is one of 14 participating institutions. The total number of study infants will be 1000 with Grade 3 or 4 IVH and 1000 matched controls. Enrollment will take place over the first four years of the study. Our site plans to enroll at total of 248 infants (124 with Gr 3 or 4 IVH and 124 matched controls) over the four year grant period. 1. For preterm neonates, IVH is attributable to a combination of environmental and genetic factors. 2. The genetic factors are alleles and haplotypes of as yet unidentified genes that render VLBW infants susceptible to IVH when born at 500 ¿¿?? 1250 g. 3. Many of these as yet unidentified genes are part of vascular, inflammatory, oxidative and/or coagulation pathways.