Joint effects of genetic variants and residential proximity to pesticide applications on hypospadias risk.
BACKGROUND
We examined risks associated with joint exposure of gene variants and pesticides.


METHODS
Analyses included 189 cases and 390 male controls born from 1991 to 2003 in California's San Joaquin Valley. We used logistic regression to examine risks associated with joint exposures of gene variants and pesticides that our previous work identified as associated with hypospadias. Genetic variables were based on variants in DGKK, genes involved in sex steroid synthesis/metabolism, and genes involved in genital tubercle development. Pesticide exposure was based on residential proximity to commercial agricultural pesticide applications.


RESULTS
Odds ratios (ORs) were highest among babies with joint exposures, who had two- to fourfold increased risks; for example, the OR was 3.7 (95% confidence interval [CI], 0.8-16.5) among subjects with the risk-associated DGKK haplotype and pesticide exposure; OR, 1.5 (95% CI, 0.7-3.1) among subjects with the haplotype and no pesticide exposure; and OR, 0.9 (95% CI, 0.5-1.6) among subjects without the haplotype but with pesticide exposure, relative to subjects with neither. However, results did not provide statistical evidence that these risks were significantly greater than expected on an additive scale, relative to risks associated with one exposure at a time.


CONCLUSIONS
We observed elevated risks associated with joint exposures to selected pesticides and genetic variants but no statistical evidence for interaction. Birth Defects Research (Part A) 106:653-658, 2016. © 2016 Wiley Periodicals, Inc.
Department of Pediatrics, Division of Neonatology and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
Suzan L
SL
Carmichael
Department of Pediatrics, Division of Neonatology and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
Wei
W
Yang
Department of Pediatrics, Division of Neonatology and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
Chen
C
Ma
Public Health Institute, Oakland, California.
Eric
E
Roberts
Pesticide Research Institute, Berkeley, California.
Susan
S
Kegley
California Department of Public Health, Richmond, California.
Paul
P
English
UCSF Benioff Children's Hospital Oakland, Oakland, California.
Edward J
EJ
Lammer
Department of Epidemiology and Biostatistics and Institute of Human Genetics, University of California, San Francisco, California.
John S
JS
Witte
Department of Pediatrics, Division of Neonatology and Developmental Medicine, Stanford University School of Medicine, Stanford, California.
Gary M
GM
Shaw
D000328:Adult; D002140:California; D016022:Case-Control Studies; D019852:Diacylglycerol Kinase / Q000235:genetics*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D015870:Gene Expression; D059647:Gene-Environment Interaction; D006239:Haplotypes; D006801:Humans; D007021:Hypospadias / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D016017:Odds Ratio; D010575:Pesticides / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000473:pathology
D010575:Pesticides; D019852:Diacylglycerol Kinase
birth defects; genes; hypospadias; pesticides; urogenital