Abstract

Description): Strong epidemiologic evidence has accumulated in recent years to suggest that periconceptional folic acid is an effective agent in reducing the occurrence and recurrence of several common congenital malformations. The metabolic and molecular basis for this preventive effect is completely unknown, and provides a unique opportunity to dissect the interacting etiologic factors that are positively affected by exogenous folic acid. The investigators designed a series of experiments to explore both the nutritional and genetic scope of folate- related factors that may interact in the etiology of neural tube and heart defects. It is hypothesized that common polymorphism in genes coding for critical enzymes in the folate pathway will interact with inadequate maternal micronutrient status to negatively affect the fetal microenvironment, and promote alterations in homeobox gene expression and tissue-specific developmental malformations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD039054-04
Application #
6653920
Study Section
Special Emphasis Panel (ZHD1-RRG-K (02))
Program Officer
Henken, Deborah B
Project Start
2000-09-25
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
4
Fiscal Year
2003
Total Cost
$760,230
Indirect Cost

  Institution

Name
Arkansas Children's Hospital Research Institute
Department
Type
DUNS #
002593692
City
Little Rock
State
AR
Country
United States
Zip Code
72202

  Publications

Nembhard, Wendy N; Tang, Xinyu; Li, Jingyun et al. (2018) A parent-of-origin analysis of paternal genetic variants and increased risk of conotruncal heart defects. Am J Med Genet A 176:609-617
Tang, Xinyu; Eberhart, Johann K; Cleves, Mario A et al. (2018) PDGFRA gene, maternal binge drinking and obstructive heart defects. Sci Rep 8:11083
Li, Ming; Li, Jingyun; He, Zihuai et al. (2016) Testing Allele Transmission of an SNP Set Using a Family-Based Generalized Genetic Random Field Method. Genet Epidemiol 40:341-51
Li, Ming; Li, Jingyun; Wei, Changshuai et al. (2016) A Three-Way Interaction among Maternal and Fetal Variants Contributing to Congenital Heart Defects. Ann Hum Genet 80:20-31
Webber, Daniel M; MacLeod, Stewart L; Bamshad, Michael J et al. (2015) Developments in our understanding of the genetic basis of birth defects. Birth Defects Res A Clin Mol Teratol 103:680-91
Tang, Xinyu; Cleves, Mario A; Nick, Todd G et al. (2015) Obstructive heart defects associated with candidate genes, maternal obesity, and folic acid supplementation. Am J Med Genet A 167:1231-42
Tai, Caroline G; Graff, Rebecca E; Liu, Jinghua et al. (2015) Detecting gene-environment interactions in human birth defects: Study designs and statistical methods. Birth Defects Res A Clin Mol Teratol 103:692-702
Tang, Xinyu; Nick, Todd G; Cleves, Mario A et al. (2014) Maternal obesity and tobacco use modify the impact of genetic variants on the occurrence of conotruncal heart defects. PLoS One 9:e108903
Li, Ming; Cleves, Mario A; Mallick, Himel et al. (2014) A genetic association study detects haplotypes associated with obstructive heart defects. Hum Genet 133:1127-38
Li, Ming; Erickson, Stephen W; Hobbs, Charlotte A et al. (2014) Detecting maternal-fetal genotype interactions associated with conotruncal heart defects: a haplotype-based analysis with penalized logistic regression. Genet Epidemiol 38:198-208

Showing the most recent 10 out of 30 publications