Diabetes Genes: Maternal Glycemia and Birth Weight

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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).