Diabetes Genes: Maternal Glycemia and Birth Weight

描述（由申请人提供）：许多研究表明低出生体重与成人2型糖尿病等慢性疾病风险之间存在联系。虽然这可能部分是由于胎儿营养改变或子宫内环境对胎儿生长的影响，但遗传因素也可能起作用。遗传因素既可以增加对疾病的易感性，也可以影响胎儿的大小。本研究将通过检验存在于母亲和/或胎儿体内的影响胰岛素敏感性或分泌（从而影响2型糖尿病风险）的遗传变异会改变胎儿生长的假设来解决这一问题。为了解决这一假设，我们已经建立了一个研究小组，他们在2型糖尿病和出生体重的遗传学、统计遗传学和胎儿环境对代谢的影响方面具有专业知识，他们将建立一个由美国国立卫生研究院和美国糖尿病协会资助的正在进行的研究，题为“高血糖和不良妊娠结局”（HAPO）。HAPO是一项多中心的国际研究，在该研究中，来自多个种族的25,000名妇女在怀孕期间血糖水平对胎儿结局的影响将被检查。正在收集参与研究的孕妇和新生儿的表型信息和DMA。目前的应用程序将利用这些资源来定义遗传变异以及这些变异与宫内环境对母体血糖和出生时大小的相互作用。具体目的如下。1)确定常见遗传变异与妊娠期间母体葡萄糖和c肽水平是否存在关联。2)确定胎儿常见遗传变异与出生体重、体重指数、头围、肥胖是否存在关联。3)确定妊娠期间与糖耐量或β细胞功能改变相关的遗传变异是否通过宫内环境或遗传因素影响胎儿发育（出生体重和肥胖）。我们将测试四组新生儿特征之间的关联：(i)母亲变异阳性和婴儿变异阴性（高风险环境和低风险遗传背景）；母亲变异呈阳性，婴儿变异呈阳性（高风险环境和遗传背景）；（iii）母亲变异阴性和婴儿变异阴性（低风险环境和遗传背景）；（iv）母亲变异阴性，婴儿变异阳性（低风险环境和高风险遗传背景）。

DESCRIPTION (provided by applicant): Many studies have demonstrated a link between low birth weight and risk of chronic diseases like type 2 diabetes in adults. Although this may result, in part, from effects of altered fetal nutrition or the environment within the uterus on the fetal growth, genetic factors may also contribute. Genetic factors could both increase susceptibility to disease and influence fetal size. This study will address this issue by examining the hypothesis that genetic variants that have an impact on insulin sensitivity or secretion (and, thus, risk for type 2 diabetes) when present in mother and/or fetus alter fetal growth. To address this hypothesis, we have established a team of investigators with expertise in the genetics of type 2 diabetes and birth weight, statistical genetics, and the impact of fetal environment on metabolism who will build upon an ongoing study funded by the NIH and American Diabetes Assoc entitled "Hyperglycemia and Adverse Pregnancy Outcome" (HAPO). HAPO is a multicenter, international study in which the impact on fetal outcome of glucose levels of 25,000 women from multiple ethnic groups during pregnancy will be examined. Phenotypic information and DMA are being collected from pregnant mothers and newborns enrolled in the study. The current application will use these resources to define genetic variants and the interactions of those variants with the intrauterine environment on maternal glycemia and size at birth. The specific aims are as follows. 1) To determine whether there is association between common genetic variation and maternal glucose and C-peptide levels measured during pregnancy. 2) To determine whether there is association between common genetic variation in the fetus and birth weight, ponderal index, head circumference, and adiposity. 3) To determine whether genetic variance associated with altered glucose tolerance or beta cell function during pregnancy impacts on fetal development (birth weight and adiposity) through the intrauterine environment or genetic factors. We will test for association between characteristics of the newborns in four groups: (i) mother variant positive and infant variant negative (high risk environment and low risk genetic background); (ii) mother variant positive and infant variant positive (high risk environment and genetic background); (iii) mother variant negative and infant variant negative (low risk environment and genetic background); (iv) mother variant negative and infant variant positive (low risk environment and high risk genetic background).