Pre-eclampsia/eclampsia (PE/E) is the most common and serious disorder of human pregnancy and is associated with substantial maternal and perinatal morbidity and mortality. There is currently no known prevention or cure for PE/E with the only effective treatment being Caesarean section, irrespective of gestation. Worldwide, the condition occurs in all major ethnic groups and eclampsia alone is responsible for over 70,000 maternal deaths annually. An assessment of its global economic importance is difficult, if not impossible. In the U.S. a conservative cost estimate in relation to caring for mothers and neonates born of mothers suffering from PE runs into several billions of dollars per annum. Like many other common human diseases there is a large genetic component underlying susceptibility to developing PE/E but the genetics are complex and not yet understood. Several groups, including ours, have provided strong evidence for PE/E susceptibility loci on chromosome 2. In the proposed next phase of the study, we will test hypotheses about the specific genes at the chromosome 2 locus we have identified to be responsible for susceptibility. The overall goal of the research is to identify the specific genes responsible for susceptibility to PE/E and to characterize the functional variants within these genes. Molecular advances in DNA sequencing and quantitative assessments of gene expression, combined with recent development of novel statistical genetic analysis make this a time of unprecedented opportunity for finding the most likely functional variants influencing susceptibility to PE/E. In this project, we will use an innovative combination of state of the science molecular and statistical genetic approaches to identify genetic determinants of susceptibility to this pregnancy disorder that persists as a major global health concern. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD049847-03
Application #
7439142
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Reddy, Uma M
Project Start
2006-09-03
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
3
Fiscal Year
2008
Total Cost
$443,511
Indirect Cost
Name
Texas Biomedical Research Institute
Department
Type
DUNS #
007936834
City
San Antonio
State
TX
Country
United States
Zip Code
78245
Yong, Hannah E J; Melton, Phillip E; Johnson, Matthew P et al. (2015) Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes. PLoS One 10:e0128230
Yong, H E J; Murthi, P; Borg, A et al. (2014) Increased decidual mRNA expression levels of candidate maternal pre-eclampsia susceptibility genes are associated with clinical severity. Placenta 35:117-24
Johnson, Matthew P; Brennecke, Shaun P; East, Christine E et al. (2012) Genome-wide association scan identifies a risk locus for preeclampsia on 2q14, near the inhibin, beta B gene. PLoS One 7:e33666
Lian, I A; Loset, M; Mundal, S B et al. (2011) Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia. Placenta 32:823-9
Johansson, Asa; Curran, Joanne E; Johnson, Matthew P et al. (2011) Identification of ACOX2 as a shared genetic risk factor for preeclampsia and cardiovascular disease. Eur J Hum Genet 19:796-800
Loset, Mari; Mundal, Siv B; Johnson, Matthew P et al. (2011) A transcriptional profile of the decidua in preeclampsia. Am J Obstet Gynecol 204:84.e1-27
Shankar, Renu; Johnson, Matthew P; Williamson, Nicholas A et al. (2010) Molecular markers of preterm labor in the choriodecidua. Reprod Sci 17:297-310
Fenstad, Mona H; Johnson, Matthew P; Roten, Linda T et al. (2010) Genetic and molecular functional characterization of variants within TNFSF13B, a positional candidate preeclampsia susceptibility gene on 13q. PLoS One 5:
Fenstad, M H; Johnson, M P; Loset, M et al. (2010) STOX2 but not STOX1 is differentially expressed in decidua from pre-eclamptic women: data from the Second Nord-Trondelag Health Study. Mol Hum Reprod 16:960-8
Fitzpatrick, E; Johnson, M P; Dyer, T D et al. (2009) Genetic association of the activin A receptor gene (ACVR2A) and pre-eclampsia. Mol Hum Reprod 15:195-204

Showing the most recent 10 out of 12 publications