Grantee Research Project Results
2005 Progress Report: Molecular Epidemiology of Hypospadias
EPA Grant Number: R828599Title: Molecular Epidemiology of Hypospadias
Investigators: Manson, Jeanne M. , Carr, Michael
Institution: Thomas Jefferson University
Current 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, 2004 through October 1, 2005
Project Amount: $2,962,288
RFA: Genetic Susceptibility and Variability of Human Malformations (1999) RFA Text | Recipients Lists
Research Category: Human Health
Objective:
The objectives of this research project are to characterize the genetic and environmental risk factors for hypospadias in the general population.
Progress Summary:
In the first 58 months of this project, a total of 218 cases, 252 affected control, and 33 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 exposures at home. Major clinical risk factors are both maternal and paternal family histories of male reproductive tract anomalies, maternal difficulty conceiving in the first pregnancy, and low birth weight. Buccal swab DNA collected from case and control infants is being assayed for any polymorphisms in the expressed portion of the SRD5A2 (steroid 5-alpha reductase type 2) gene, the 17βHSD3 (17β hydroxysteroid dehydrogenase type 3) gene, and trinucleotide repeats on the AR (androgen receptor) gene. Several common single nucleotide polymorphisms (SNPs) in exon 1 of the SRD5A2 gene have been identified: V89L and A49T. Both SNPs are known to be functionally significant in altering enzyme activity. Cases do not have a higher proportion of the variant L allele in V89L, whereas a significantly higher proportion of the variant T allele in A49T has been associated with severity of 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. Efforts will continue to evaluate the relationship between trinucleotide repeats in the AR gene and the risks for hypospadias, and no further efforts will be made to evaluate the 17β HSD3 gene.
Future Activities:
In the next year, we plan to consent an additional 240 families to obtain 180 new families enrolled in the study. This will result in a final group size of approximately 711 families. Gene analysis for SNPs in SRD5A2 and for trinucleotide repeats on the androgen receptor should be completed on the entire cohort. There should be sufficient data for final evaluation of genetic and environmental risk factors for hypospadias.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 39 publications | 7 publications in selected types | All 7 journal articles |
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Barthold JS, Manson J, Regan V, Si X, Hassink SG, Coughlin MT, Lee PA. Reproductive hormone levels in infants with cryptorchidism during postnatal activation of the pituitary-testicular axis. The Journal of Urology 2004;172(4 Pt 2):1736-1741. |
R828599 (2005) R828599 (2006) R828599 (Final) |
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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, children’s health, environmental chemistry, health risk assessment, genetic susceptibility, environmental toxicant, hypospadias, maternal exposure, prenatal exposure, endocrine disruptors,, Health, RFA, Scientific Discipline, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Biology, genetic susceptability, Environmental Chemistry, Children's Health, Biochemistry, Human Health Risk Assessment, infants, epidemeology, male infants, pregnancy, maternal exposure, molecular epidemeology, prenatal exposure, children, endocrine disruptors, toxics, children's vulnerablity, environmental toxicant, assessment of exposure, 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.