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.
