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). ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK067459-03
Application #
7409742
Study Section
Special Emphasis Panel (ZRG1-KNOD-N (01))
Program Officer
Mckeon, Catherine T
Project Start
2006-04-15
Project End
2010-04-14
Budget Start
2008-04-15
Budget End
2010-04-14
Support Year
3
Fiscal Year
2008
Total Cost
$221,677
Indirect Cost
Name
Northwestern University at Chicago
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Urbanek, Margrit; Hayes, M Geoffrey; Armstrong, Loren L et al. (2013) The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study. Hum Mol Genet 22:3583-96
Ackerman, C M; Lowe, L P; Dyer, A R et al. (2013) Maternal testosterone levels are associated with C-peptide levels in the Mexican American subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study cohort. Horm Metab Res 45:617-20
Hayes, M Geoffrey; Urbanek, Margrit; Hivert, Marie-France et al. (2013) Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes 62:3282-91
Urbanek, Margrit; Hayes, M Geoffrey; Lee, Hoon et al. (2012) The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy. PLoS One 7:e32958
Ackerman, Christine M; Lowe, Lynn P; Lee, Hoon et al. (2012) Ethnic variation in allele distribution of the androgen receptor (AR) (CAG)n repeat. J Androl 33:210-5
Freathy, Rachel M; Hayes, M Geoffrey; Urbanek, Margrit et al. (2010) Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the I Diabetes 59:2682-9
Ackerman, C M; Lowe, L P; Lee, H et al. (2010) The role of the polycystic ovary syndrome susceptibility locus D19S884 allele 8 in maternal glycemia and fetal size. J Clin Endocrinol Metab 95:3242-50