Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes

Abstract

The paraoxonase 1 (PON1) enzyme prevents low-density lipoprotein oxidation and also detoxifies the oxon derivatives of certain neurotoxic organophosphate (OP) pesticides. PON1 activity in infants is low compared to adults, rendering them with lower metabolic and antioxidant capacities. We made a longitudinal comparison of the role of genetic variability on control of PON1 phenotypes in Mexican-American mothers and their children at the time of delivery (n=388 and 338, respectively) and again 7 years later (n=280 and 281, respectively) using generalized estimating equations models. At age 7, children's mean PON1 activities were still lower than those of mothers. This difference was larger in children with genotypes associated with low PON1 activities (PON1(-108TT), PON1(192QQ), and PON1(-909CC)). In mothers, PON1 activities were elevated at delivery and during pregnancy compared to 7 years later when they were not pregnant (p<0.001). In non-pregnant mothers, PON1 polymorphisms and haplotypes accounted for almost 2-fold more variation of arylesterase (AREase) and chlorpyrifos-oxonase (CPOase) activity than in mothers at delivery. In both mothers and children, the five PON1 polymorphisms (192, 55, -108, -909, -162) explained a noticeably larger proportion of variance of paraoxonase activity (62-78%) than AREase activity (12.3-26.6%). Genetic control of PON1 enzymatic activity varies in children compared to adults and is also affected by pregnancy status. In addition to known PON1 polymorphisms, unidentified environmental, genetic, or epigenetic factors may also influence variability of PON1 expression and therefore susceptibility to OPs and oxidative stress.

Figure 1

The distribution of AREase in the CHAMACOS children at birth, age 2, and age seven and in their mothers during pregnancy (26 weeks gestation), at the time of delivery, and when their children were seven years old. Mean AREase activities as indicated by the grey horizontal bars, were 33.1, 89.2, 121.5 U/mL in children at birth, 2, and 7 years of age, respectively. In mothers, mean AREase activities were 129.1, 136.3, and 127.3 U/mL at pregnancy, delivery and seven years later, respectively. PON1 enzymatic activity was very low in newborns and continued to increase over time. At age seven, activities were still significantly lower than that of mothers at the same time point (p= 0.05). PON1 activities were elevated in mothers at the time of delivery (p<0.0005). This figure contains some of the children’s PON1 activity data (children at age two) modified from Huen et al. (2009a).