This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Fetal growth restriction (also referred to as intrauterine growth restriction), is a complex, pleiotropic condition and is associated with significant newborn mortality and morbidity. Previous studies have shown that birth weight varies by ethnicity and that fetal growth restriction (FGR) disproportionately affects African Americans and other ethnic minorities in the United States. The long term goal of this study is to identify and understand the molecular mechanisms associated with FGR as well as the unique mechanisms that contribute to ethnic disparities in the incidence of FGR. This work may lead to novel means of therapeutic intervention as well as new methods for diagnostic and prognostic testing. While maternal poverty, stress, nutrition, and environmental exposures certainly play a role, the molecular mechanisms which mediate growth restrictions are poorly understood. In addition, single gene and polygenic disorders are likely to cause fetal growth disorders, and the incidence of these mutations is likely to vary by ethnic group. One exciting observation is that telomerase, an enzymatic complex required to maintain the stability of chromosome ends and prevent cell senescence, is suppressed in the placenta of infants with asymmetric FGR. Our specific hypothesis is that telomerase defects underlie many cases of idiopathic FGR, especially those with accelerated placental maturation.
The specific aims of this study are as follows:
Specific Aim 1 : Establish a modern and comprehensive characterization of fetal growth restriction using clinical data, anthropometric assessment, and molecular techniques for known etiologies. We will determine the 'phenotype' of idiopathic infants to allow appropriate comparisons, and discover which subcategories are responsible for health disparities in ethnic minorities in Hawai'i.
Specific Aim 2 : Assess the role of telomerase suppression and accelerated telomere shortening in the placenta as a potential cause of fetal growth restriction and determine whether polymorphisms or expression differences in TR and TERT play a role in ethnic differences amongst ethnic groups in Hawai`i.The study will utilize de-identified tissue samples and clinical data from the Pacific Research Center for Early Human Development (PRCEHD), Clinical Phenotype/Patient Sample Core, directed by Kenneth Ward, M.D. CRC support is requested to coordinate with the PRCEHD on acquisition of the samples and clinical data.
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