Prenatal pesticide exposure interacts with a common polymorphism in the PON1 gene leading to cardiometabolic risk profile in childhood
Tuesday, November 5, 2013
Background: Prenatal environmental exposures may influence the risk of developing cardiometabolic disease later in life. The HDL-associated anti-oxidative enzyme paraoxonase 1 (PON1) may protect against atherosclerosis and also hydrolyze environmental chemicals, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties. The aim of this study was to examine if the PON1 Q192R genotype affects cardiometabolic risk factors in school-age children prenatally exposed to pesticides. Methods: Pregnant women working in greenhouses were categorized as high, medium, or not occupationally exposed to pesticides. At age 6 to11 years, their children underwent a standardized physical examination where blood pressure, skin folds, and other anthropometric parameters were measured. Exposure status was unknown to the examiner. PON1-genotype was determined for 141 children (88 pesticide-exposed and 53 unexposed). Non-fasting serum was analyzed for IGF-1, IGFBP3, insulin, and leptin. Results: Exposed children carrying the PON1 R-allele had higher blood pressure, BMI, abdominal circumference, body fat percentage, and serum concentrations of leptin and IGF-1 than did unexposed children. The effects were associated with the prenatal pesticide exposure level. In contrast, children with the PON1 192 QQ genotype showed no significant effect in these outcomes in regard to prenatal pesticide exposure. Conclusion: Our results suggest a gene-environment interaction between prenatal pesticide exposure and the PON1 genotype that affects cardiometabolic risk markers already known to be associated with the PON1 192 R-allele. The results also illustrate that a hypersusceptible subgroup of the population may be more seriously affected, although average effects may not be evident in the entire population.
Environmental health sciences
Occupational health and safety
Describe why some children are likely to be more sensitive to prenatal exposure
Explain the importance of including gene-environment interaction in risk assessment and prevention
Keyword(s): Genetics, Pesticide Exposure
Presenting author's disclosure statement:
Qualified on the content I am responsible for because: I have been the principal or co-principal of several epidemiological studies on exposure to pesticides and endocrine disruptors (EDCs) and associated health effects. Among my scientific interests is identification of susceptible population groups to improve prevention of environmentally related health effects.
Any relevant financial relationships? No
I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines,
and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed
in my presentation.