Longitudinal changes in PON1 enzymatic activities in Mexican-American mothers and children with different genotypes and haplotypes.
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.
Huen
Karen
K
Center for Children's Environmental Health, 50 University Hall, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.
Harley
Kim
K
Bradman
Asa
A
Eskenazi
Brenda
B
Holland
Nina
N
D000328:Adult; D043303:Aryldialkylphosphatase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D002648:Child; D015331:Cohort Studies; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D017058:Mexican Americans / Q000235:genetics*; D010755:Organophosphates / Q000008:administration & dosage; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
D010755:Organophosphates; D043303:Aryldialkylphosphatase