Grantee Research Project Results
2004 Progress Report: Molecular Epidemiology of Hypospadias
EPA Grant Number: R828599Title: Molecular Epidemiology of Hypospadias
Investigators: Manson, Jeanne M. , Carr, Michael
Institution: The Children's Hospital of Philadelphia
EPA Project Officer: Aja, Hayley
Project Period: July 1, 2002 through October 1, 2007
Project Period Covered by this Report: July 1, 2003 through October 1, 2004
Project Amount: $2,962,288
RFA: Genetic Susceptibility and Variability of Human Malformations (1999) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The objective of this research project is to characterize the genetic and environmental risk factors for hypospadias in the general population.
Progress Summary:
In the first 47 months of this project, a total of 187 case families, 206 affected control families, and 23 unaffected control families have been enrolled. The case and control groups are well balanced in terms of race/ethnicity and demographics. Environmental risk factors identified to date for hypospadias are paternal and maternal pesticide exposures at home and maternal paints/stain exposure at home. The major clinical risk factor is low birth weight. Buccal swab DNA collected from case and control infants is being assayed for any polymorphisms in the expressed portion of the steroid 5-alpha reductase type 2 (SRD5A2) gene, the 17β hydroxysteroid dehydrogenase type 3 (17β HSD3) gene, and trinucleotide repeats on the androgen receptor (AR) gene. A common single nucleotide polymorphism (SNP) in exon 1 of the SRD5A2 gene (V89L) has been identified, and a significant association of the L allele with severity of hypospadias has been found. Efforts will continue to assess the relationship between this SNP and the risks for hypospadias. There have been no significant associations found between trinucleotide repeat lengths on the AR and risks for hypospadias, nor in allelic variants in the 17β HSD3 gene. No further efforts will be made to evaluate these genes.
Future Activities:
We will complete gene analysis for SRD5A2 on the entire cohort.In the next year, there should be approximately 180 additional families enrolled in the study, giving approximately 600 families out of a total of 800. There should be sufficient data for final evaluation of genetic and environmental risk factors for hypospadias.
Journal Articles on this Report : 1 Displayed | Download in RIS Format
| Other project views: | All 39 publications | 7 publications in selected types | All 7 journal articles |
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Manson JM, Carr MC. Molecular epidemiology of hypospadias: review of genetic and environmental risk factors. Birth Defects Research Part A:Clinical and Molecular Teratology 2003;67(10):825-836. |
R828599 (2002) R828599 (2003) R828599 (2004) R828599 (2005) R828599 (2006) R828599 (Final) |
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Supplemental Keywords:
infant, epidemiology, genetic, urogenital, DNA, environmental risk factors, polymorphism, hypospadias, health, biochemistry, biology, children’s health, environmental chemistry, risk assessment, susceptibility/sensitive population/genetic susceptibility, human health risk assessment, assessment of exposure, children, children’s vulnerability, developmental disorders, endocrine disruptors, environmental toxicant, human susceptibility, male infants, maternal exposure, molecular epidemiology, pregnancy, prenatal exposure,, Health, RFA, Scientific Discipline, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Biology, genetic susceptability, Environmental Chemistry, Children's Health, Biochemistry, epidemeology, Human Health Risk Assessment, male infants, infants, maternal exposure, pregnancy, molecular epidemeology, prenatal exposure, children, children's vulnerablity, endocrine disruptors, toxics, assessment of exposure, environmental toxicant, human susceptibility, developmental disordersProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.