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Background  Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism,  PON1  Q192R, affects both properties, but a potential interaction between  PON1  genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the  PON1  Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides.    Methods  Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured.  PON1 -genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores.    Results  Prenatally pesticide exposed children carrying the  PON1  192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the  PON1  192QQ genotype, none of the variables was affected by prenatal pesticide exposure.    Conclusion  Our results indicate a gene-environment interaction between prenatal pesticide exposure and the  PON1  gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele.

Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age