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

نویسندگان

  • Karen Huen
  • Kim Harley
  • Asa Bradman
  • Brenda Eskenazi
  • Nina Holland
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Short Communication Haplotype-Phenotype Relationships of Paraoxonase-1

Paraoxonase 1 (PON1) is an enzyme with multiple activities, including detoxification of organophosphates. It is believed to be important in preventing neurotoxic damage and has also been implicated in atherosclerosis. The PON1 gene contains five common polymorphisms, three in the promoter ( 909G > C, 162A > G, 108C > T) and two in the coding region (M55L, Q192R) with varying but incomplete link...

متن کامل

Paraoxonase Polymorphisms, Haplotypes, and Enzyme Activity in Latino Mothers and Newborns

Recent studies have demonstrated widespread pesticide exposures in pregnant women and in children. Plasma paraoxonase 1 (PON1) plays an important role in detoxification of various organophosphates. The goals of this study were to examine in the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort of Latina mothers and their newborns living in the Salinas Valle...

متن کامل

Effects of PON polymorphisms and haplotypes on molecular phenotype in Mexican-American mothers and children.

Paraoxonase 1 (PON1) prevents oxidation of low-density lipoproteins and inactivates toxic oxon derivatives of organophosphate pesticides (OPs). More than 250 SNPs have been previously identified in the PON1 gene, yet studies of PON1 genetic variation focus primarily on a few promoter SNPs (-108, -162) and coding SNPs (192, 55). We sequenced the PON1 gene in 30 subjects from a Mexican-American b...

متن کامل

Paraoxonase Activities in Metabolic Syndrome in Children and Adolescents

Background: Metabolic syndrome (MetS) is a collection of various interrelated risk factors that appear to have an impact as development of atherosclerotic cardiovascular disease (CVDs). Epidemic of childhood and adolescent&rsquo;s obesity has increased interest in the metabolic syndrome (MS) due to the potential projection into adulthood. The prevalence of MS in adolescents has been estimated t...

متن کامل

Association of Organophosphate Pesticide Exposure and Paraoxonase with Birth Outcome in Mexican-American Women

BACKGROUND Epidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association. METHODS The study population included 470 pregnant women enrolled in the CHAMACOS Study, a ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Toxicology and applied pharmacology

دوره 244 2  شماره 

صفحات  -

تاریخ انتشار 2010