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

Journal Article · Thu Apr 15 04:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.12.031· OSTI ID:21344919

Huen, Karen; Harley, Kim; Bradman, Asa; Eskenazi, Brenda ^[1]; Holland, Nina ^[1]

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1. Center for Children's Environmental Health, 50 University Hall, School of Public Health, University of California, Berkeley, CA 94720-7360 (United States)

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{sub -108TT}, PON1{sub 192QQ}, and PON1{sub -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.

• OSTI ID: 21344919
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 244; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADULTS
AGE GROUPS
ANIMALS
ANTIOXIDANTS
BIOLOGICAL VARIABILITY
CHEMICAL REACTIONS
CHILDREN
CONTROL
ENZYMES
GENETIC CONTROL
GENETIC VARIABILITY
GENOTYPE
INFANTS
LIPIDS
LIPOPROTEINS
MAMMALS
MAN
ORGANIC COMPOUNDS
OXIDATION
PEST CONTROL
PESTICIDES
PHENOTYPE
PREGNANCY
PRIMATES
PROTEINS
STRESSES
VERTEBRATES