Association between PON1 genetic polymorphisms and miscarriage in Mexican women exposed to pesticides

BackgroundPlacental oxidative stress has been involved in the pathogenesis of certain reproductive adverse effects, including miscarriage. Paraxonase 1 (PON1) is a high-density lipoprotein(HDL)-linked enzyme that prevents oxidation of low-density lipoproteins (LDL) and is involved in detoxification from organophosphate pesticides.ObjectiveTo assess the association between maternal PON1 polymorphisms (PON1192Q/R, PON155 L/M y PON1− 108C/T) and the risk of miscarriage in women chronically exposed to organophosphate pesticides in Mexico.MethodsIn a cross-sectional study, socio-demographic data, reproductive history data, environmental exposures, and other variables of concern were collected by means of a questionnaire from 264 women (floriculturists and wives of floriculturists) who had been pregnant sometime during the 10 years preceding the study. Blood samples were also collected from them. PON1192 and PON155 genotypes were determined by PCR amplification, and PON1− 108 genotypes, by a TaqMan real-time polymerase chain reaction assay. Complete information regarding the results of pregnancy and maternal genotype tests was obtained for 514 pregnancies (35 miscarriages and 479 controls). The association between PON1 genotypes and miscarriage was evaluate through GEE models.ResultsThe risk of miscarriage by mothers with PON1192RR genotype was 2.2 higher than by mothers with PON1192QR/PON1192QQ genotype (95% CI 0.93–5.17). The risk was close to 4 times higher in mothers with PON155MM/PON155LM genotype than in mothers with PON155LL genotype (OR = 3.9; 95% CI 1.38–11.0). No significant differences were found in risk of miscarriage based on the maternal PON1− 108C/T genotype. No evidence was found of an interaction between the various PON1 genotypes and the mothers' floricultural activity during pregnancy.ConclusionsThis study suggests that there is an effect of genetic maternal PON1 polymorphisms on miscarriage and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in utero.

► We evaluated the association between maternal PON1 polymorphisms (PON1192Q/R, PON155 L/M y PON1− 108C/T) and the risk of miscarriage in women chronically exposed to organophosphate pesticides in Mexico.
► The risk of miscarriage by mothers with PON1192RR genotype was 2.2 higher than by mothers with PON1192QR/PON1192QQ genotype.
► The risk close to 4 times higher in mothers with PON155MM / PON155LM than in mothers with PON155LL genotype.
► This study suggests that there is an effect of genetic maternal PON1 polymorphisms on miscarriage.