Maternal Vasoactive Exposures and Risk of Clubfoot

母体血管活性物质暴露和马蹄内翻足的风险

• 批准号: 7582685
• 负责人: MARTHA M. WERLER
• 金额: $ 7.65万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-20 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7582685
• 关键词: Address; Apoptosis; Apoptotic; Candidate Disease Gene; Congenital Abnormality; Congenital clubfoot; DNA; Data Set; Development; Enzymes; Etiology; Family Study; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Grant; Growth Factor; Homeobox; IGFBP3 gene; Infant; Insulin; Interview; Laboratories; Link; Live Birth; Metabolic Biotransformation; Mothers; NAT2 gene; Odds Ratio; Parents; Pathogenesis; Pathway interactions; Play; Population Study; Pregnancy; Prevention; Research Personnel; Resources; Risk; Role; Saliva; Sampling; Signal Transduction; Smoke; Testing; Transferase; Translating; Variant; cigarette smoking; cigarette smoking; experience; gene discovery; genetic risk factor; genetic variant; malformation; maternal cigarette smoking; public health relevance

DESCRIPTION (provided by investigator): Talipes equinovarus or clubfoot occurs in approximately one of every 1000 live births. Although it is one of the most common structural malformations, little is known about its etiology. There is strong evidence to suggest that genetic factors play a role in the development of clubfoot. In a separate study population, our investigative team has identified candidate genes for clubfoot in the homeobox signaling, program cell death, insulin growth factor, and n-acetyl transferase pathways. Further, maternal cigarette smoking has been linked to clubfoot in several studies, and this association may be well be modified by n-acetyl transferase genotypes because this enzyme is involved in the biotransformation of the byproducts of cigarette smoke. In the parent study, DNA is collected from baby and mother with Oragene saliva kits. However, the parent study included no specific aims or funding to examine DNA for genetic risk factors. This application aims to study genetic variation in candidate genes, which were previously shown to be associated with clubfoot in family studies. The candidate genes will be identified in a separate study of clubfoot which has currently identified associations between clubfoot and variation in HoxA, HoxD, IGFBP3 and apoptotic pathway genes. In addition, three functional polymorphisms in NAT2 will be evaluated to look for an interaction with maternal smoking and the risk of clubfoot. Saliva samples will be available on over 400 clubfoot cases and their mothers and over 900 control mother-baby pairs. Mothers are interviewed within one year after delivery and detailed information is collected on cigarette smoking. We anticipate >80 per cent statistical power to detect slight differences for polymorphisms and 2.5-fold odds ratios for gene-smoking interaction. This supplement will provide the resources to test this powerful dataset for genetic and environmental causes of clubfoot and will yield important information that will translate into better management of clubfoot. PUBLIC HEALTH RELEVANCE: Clubfoot is one of the most common congenital malformations but its causes are not known. The aims of this supplemental grant are to identify genetic factors, as well as gene-smoking interactions, in relation to risk of clubfoot. Our goal is to understand the etiology and pathogenesis of clubfoot, leading to prevention.

描述（调查员提供）：Talipes Equinovarus或Clubfoot发生在每1000个活产中的大约一次。尽管它是最常见的结构畸形之一，但对其病因知之甚少。有强有力的证据表明，遗传因素在俱乐部长足的发展中起作用。在另一项研究人群中，我们的调查小组在同型信号传导，程序细胞死亡，胰岛素生长因子和N-乙酰基转移酶途径中确定了Clubfoot的候选基因。此外，在几项研究中，孕产妇的吸烟与俱乐部的俱乐部有关，N-乙酰基转移酶基因型可能会经过修改，因为该酶参与了香烟烟雾的副产品的生物转化。在父母的研究中，DNA是从婴儿和母亲的Oragene唾液套件中收集的。但是，父母的研究没有任何特定的目标或资金来检查DNA是否有遗传危险因素。该应用程序旨在研究候选基因的遗传变异，这些基因以前被证明与家庭研究中的俱乐部有关。候选基因将在俱乐部长足的单独研究中鉴定出来，该研究目前已经确定了俱乐部长足与HOXA，HOXD，IGFBP3和凋亡途径基因的变化之间的关联。此外，还将评估NAT2中三种功能多态性，以寻找与孕产妇吸烟和俱乐部脚步风险的相互作用。唾液样本将在400多个俱乐部案例及其母亲以及900多个对照母亲双子室中提供。分娩后一年内接受了母亲的采访，并收集了有关吸烟的详细信息。我们预计统计能力> 80％，可以检测到多态性的轻微差异和2.5倍的基因吸烟相互作用的比值比。该补充剂将提供资源来测试该强大的数据集以构成俱乐部的遗传和环境原因，并产生重要的信息，这些信息将转化为更好地管理俱乐部俱乐部。公共卫生相关性：俱乐部俱乐部是最常见的先天性畸形之一，但其原因尚不清楚。这种补充赠款的目的是确定与俱乐部的风险有关的遗传因素以及吸烟的相互作用。我们的目标是了解俱乐部长足的病因和发病机理，从而导致预防。