This proposal is in response to PA PAR-99-027 """"""""Mentored Research Scientist Development Award in Molecular Epidemiology. """""""" The rapid completion of the Human Genome Project along with recent advances in molecular biology and genetics have generated a tremendous opportunity for environmental health researchers to elucidate how genetic variants affect individual responses to environmental exposures. Multi-disciplinary scientists trained in epidemiological as well as molecular and genetic methodologies are needed to utilize this opportunity. The overall goal of this proposal is to support the mentored research career development of Dr. Scott Venners in molecular and genetic epidemiology in the context of an investigation of genetic influences on the risk of adverse reproductive outcomes in men and women who are exposed to parathion, an organophosphate pesticide. This proposal will utilize existing epidemiological and clinical data as well as blood specimens from a large prospective cohort study in Anqing, China, funded by NIEHS (ES08957) to evaluate the effects of organophosphate pesticide exposure on reproductive outcomes. Detailed exposure information will be available as well as information on the following outcomes of interest: (in men) sperm parameters (sperm concentration, total count, motility and morphology); and (in women) menstrual disorders, infertility, early fetal loss, spontaneous abortion, preterm delivery, low birthweight and intrauterine growth retardation (IUGR). Dr. Venners will test the association between selected candidate genes and adverse reproductive outcomes in the study population including analyses of gene-environment interaction and using haplotype based linkage disequilibrium analysis. Specifically, Dr. Venners will assess 10 candidate genes relevant both to metabolism of organophosphate pesticide and endocrine function including: CYP3A4, PON1, PON2, PON3, GSTM1, BCHE, ESR1, GnRHR LHCGR, and FSHR. Dr. Venners will investigate SNPs included in the NIEHS GeneSNP database as well as others identified from the literature. A total of 1000 husband-wife pairs (2000 subjects) will be genotyped using PCR-OLA/PCR-RFLP assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01ES012052-04
Application #
7057220
Study Section
Environmental Health Sciences Review Committee (EHS)
Program Officer
Shreffler, Carol K
Project Start
2004-04-23
Project End
2008-02-28
Budget Start
2006-06-15
Budget End
2007-02-28
Support Year
4
Fiscal Year
2006
Total Cost
$108,441
Indirect Cost
Name
University of Illinois at Chicago
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Tollner, Theodore L; Venners, Scott A; Hollox, Edward J et al. (2011) A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med 3:92ra65
Perry, Melissa J; Venners, Scott A; Chen, Xing et al. (2011) Organophosphorous pesticide exposures and sperm quality. Reprod Toxicol 31:75-9
Yu, Yunxian; Venners, Scott A; Wang, Binyan et al. (2010) Association of central adiposity with prediabetes and decreased insulin sensitivity in rural Chinese normal-weight and overweight women. Metabolism 59:1047-53
Ouyang, Fengxiu; Necheles, Jonathan; Wang, Binyan et al. (2009) Association of surrogate and direct measures of adiposity with risk of metabolic syndrome in rural Chinese women. Eur J Nutr 48:323-32
Ronnenberg, Alayne G; Venners, Scott A; Xu, Xiping et al. (2007) Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol 166:304-12
Yu, Yunxian; Kumar, Rajesh; Venners, Scott et al. (2007) Age and gender specific lung function predictive equations provide similar predictions for both a twin population and a general population from age 6 through adolescence. Pediatr Pulmonol 42:631-9
Venners, Scott A; Liu, Xue; Perry, Melissa J et al. (2006) Urinary estrogen and progesterone metabolite concentrations in menstrual cycles of fertile women with non-conception, early pregnancy loss or clinical pregnancy. Hum Reprod 21:2272-80
Venners, Scott A; Korrick, Susan; Xu, Xiping et al. (2005) Preconception serum DDT and pregnancy loss: a prospective study using a biomarker of pregnancy. Am J Epidemiol 162:709-16