Lead Exposure Is Associated with Decreased Serum Paraoxonase 1 (PON1) Activity and Genotypes

Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, −108C/T). The mean blood lead level (± SD) of this cohort was 27.1 ± 15 μg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p < 0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele

Organophosphate Pesticide Exposure and Neurobehavioral Performance in Agricultural and Nonagricultural Hispanic Workers

Our understanding of the health risks of farmworkers exposed to pesticides in their work and home environments is rapidly increasing, although studies designed to examine the possible neurobehavioral effects of low-level chronic pesticide exposure are limited. We measured dialkyl phosphate urinary metabolite levels, collected environmental dust samples from a subset of homes, obtained information on work practices, and conducted neurobehavioral tests on a sample of farmworkers in Oregon. Significant correlations between urinary methyl metabolite levels and total methyl organophosphate (azinphos-methyl, phosmet, malathion) house dust levels were observed. We found the neurobehavioral performance of Hispanic immigrant farmworkers to be lower than that observed in a nonagricultural Hispanic immigrant population, and within the sample of agricultural workers there was a positive correlation between urinary organophosphate metabolite levels and poorer performance on some neurobehavioral tests. These findings add to an increasing body of evidence of the association between low levels of pesticide exposure and deficits in neurobehavioral performance

Organophosphate Pesticide Exposure and Neurodevelopment in Young Mexican-American Children

BACKGROUND: Organophosphate (OP) pesticides are widely used in agriculture and homes. Animal studies suggest that even moderate doses are neurodevelopmental toxicants, but there are few studies in humans. OBJECTIVES: We investigated the relationship of prenatal and child OP urinary metabolite levels with children’s neurodevelopment. METHODS: Participating children were from a longitudinal birth cohort of primarily Latino farm-worker families in California. We measured six nonspecific dialkylphosphate (DAP) metabolites in maternal and child urine as well as metabolites specific to malathion (MDA) and chlorpyrifos (TCPy) in maternal urine. We examined their association with children’s performance at 6 (n = 396), 12 (n = 395), and 24 (n = 372) months of age on the Bayley Scales of Infant Development [Mental Development (MDI) and Psychomotor Development (PDI) Indices] and mother’s report on the Child Behavior Checklist (CBCL) (n = 356). RESULTS: Generally, pregnancy DAP levels were negatively associated with MDI, but child measures were positively associated. At 24 months of age, these associations reached statistical significance [per 10-fold increase in prenatal DAPs: β = −3.5 points; 95% confidence interval (CI), −6.6 to −0.5; child DAPs: β = 2.4 points; 95% CI, 0.5 to 4.2]. Neither prenatal nor child DAPs were associated with PDI or CBCL attention problems, but both prenatal and postnatal DAPs were associated with risk of pervasive developmental disorder [per 10-fold increase in prenatal DAPs: odds ratio (OR) = 2.3, p = 0.05; child DAPs OR = 1.7, p = 0.04]. MDA and TCPy were not associated with any outcome. CONCLUSIONS: We report adverse associations of prenatal DAPs with mental development and pervasive developmental problems at 24 months of age. Results should be interpreted with caution given the observed positive relationship with postnatal DAPs

Developmental Changes in PON1 Enzyme Activity in Young Children and Effects of PON1 Polymorphisms

BackgroundParaoxonase 1 (PON1) is an enzyme that detoxifies activated organophosphorus pesticides (OPs) and is also involved in oxidative stress pathways.ObjectivesPON1 activity in newborns is lower than in adults, but the ontogeny of PON1 activity is poorly characterized in young children. We examined the effects of age and PON1 genotype on enzyme activity in a birth cohort of Mexican-American children.MethodsWe determined three substrate-specific measures of PON1 activity in 1,143 plasma samples collected longitudinally from 458 children at five time points from birth through 7 years of age, and genotyped PON1 polymorphisms at positions 192 and -108 in these children.ResultsContrary to previous reports that PON1 activities plateau by 2 years of age, we observed an age-dependent increase in all three PON1 measures from birth through 7 years of age (p &lt; 0.0001). The PON1(192) genotype significantly modified the effect of age on paraoxonase (POase) activity (p &lt; 0.0001) such that increases in enzyme activity with age were influenced by the number of R alleles in a dose-dependent manner. Children with the PON1(-108CC192RR) diplotype had significantly higher mean PON1 activities and also experienced steeper increases of POase activity over time compared with children with the PON1(-108TT192QQ) diplotype.ConclusionsLower levels of the PON1 enzyme, which is involved in protection against OPs and oxidative stress, persist in young children past 2 years of age through at least 7 years of age. Future policies addressing pesticide exposure in children should take into account that the window of vulnerability to OPs in young children may last beyond infancy

PON1 and Neurodevelopment in Children from the CHAMACOS Study Exposed to Organophosphate Pesticides in Utero

BackgroundParaoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.ObjectiveWe determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.MethodsWe measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds' blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.ResultsChildren with the PON1(-108T) allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1(-108T) allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.ConclusionPON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure

Comparing the health of low income and less well educated groups in the United States and Canada

<p>Abstract</p> <p>Background</p> <p>A limited number of health status and health-related quality of life (HRQL) measures have been used for inter-country comparisons of population health. We compared the health of Canadians and Americans using a preference-based measure.</p> <p>Methods</p> <p>The Joint Canada/United States Survey of Health (JCUSH) 2002–03 conducted a comprehensive cross-sectional telephone survey on the health of community-dwelling residents in Canada and the US (n = 8688). A preference-based measure, the Health Utilities Index Mark 3 (HUI3), was included in the JCUSH. Health status was analyzed for the entire population and white population only in both countries. Mean HUI3 overall scores were compared for both countries. A linear regression determinants of health model was estimated to account for differences in health between Canada and the US. Estimation with bootstraps was used to derive variance estimates that account for the survey's complex sampling design of clustering and stratification.</p> <p>Results</p> <p>Income is associated with health in both countries. In the lowest income quintile, Canadians are healthier than Americans. At lower levels of education, again Canadians are healthier than Americans. Differences in health among subjects in the JCUSH are explained by age, gender, education, income, marital status, and country of residence.</p> <p>Conclusion</p> <p>On average, population health in Canada and the US is similar. However, health disparities between Canadians and Americans exist at lower levels of education and income with Americans worse off. The results highlight the usefulness of continuous preference-based measures of population health such as the HUI3.</p

Paraoxonase 1 (PON1) Polymorphisms, Haplotypes and Activity in Predicting CAD Risk in North-West Indian Punjabis

Human serum paraoxonase-1 (PON1) prevents oxidation of low density lipoprotein cholesterol (LDL-C) and hydrolyzes the oxidized form, therefore preventing the development of atherosclerosis. The polymorphisms of PON1 gene are known to affect the PON1 activity and thereby coronary artery disease (CAD) risk. As studies are lacking in North-West Indian Punjabi's, a distinct ethnic group with high incidence of CAD, we determined PON1 activity, genotypes and haplotypes in this population and correlated them with the risk of CAD.350 angiographically proven (≥ 70% stenosis) CAD patients and 300 healthy controls were investigated. PON1 activity was determined towards paraoxon (Paraoxonase; PONase) and phenylacetate (Arylesterase; AREase) substrates. In addition, genotyping was carried out by using multiplex PCR, allele specific oligonucleotide -PCR and PCR-RFLP methods and haplotyping was determined by PHASE software. The serum PONase and AREase activities were significantly lower in CAD patients as compared to the controls. All studied polymorphisms except L55M had significant effect on PONase activity. However AREase activity was not affected by them. In a logistic regression model, after adjustment for the conventional risk factors for CAD, QR (OR: 2.73 (1.57-4.72)) and RR (OR, 16.24 (6.41-41.14)) genotypes of Q192R polymorphism and GG (OR: 2.07 (1.02-4.21)) genotype of -162A/G polymorphism had significantly higher CAD risk. Haplotypes L-T-G-Q-C (OR: 3.25 (1.72-6.16)) and L-T-G-R-G (OR: 2.82 (1.01-7.80)) were also significantly associated with CAD.In conclusion this study shows that CAD patients had lower PONase and AREase activities as compared to the controls. The coding Q192R polymorphism, promoter -162A/G polymorphism and L-T-G-Q-C and L-T-G-R-G haplotypes are all independently associated with CAD

A comparative analysis of chiropractic and general practitioner patients in North America: Findings from the joint Canada/United States survey of health, 2002–03

BACKGROUND: Scientifically rigorous general population-based studies comparing chiropractic with primary-care medical patients within and between countries have not been published. The objective of this study is to compare care seekers of doctors of chiropractic (DCs) and general practitioners (GPs) in the United States and Canada on a comprehensive set of sociodemographic, quality of life, and health-related variables. METHODS: Data are from the Joint Canada/U.S. Survey of Health (JCUSH), 2002–03, a random sample of adults in Canada (N = 3505) and the U.S. (N = 5183). Respondents were categorized according to their pattern of health-care use in the past year. Distributions, percentages, and estimates (adjusted odds ratios) weighted to reflect the complex survey design were produced. RESULTS: Nearly 80% of respondents sought care from GPs; 12% sought DC care. Compared with GP only patients, DC patients in both countries tend to be under 65 and white, with arthritis and disabling back or neck pain. U.S. DC patients are more likely than GP only patients to be obese and to lack a regular doctor; Canadian DC patients are more likely than GP only patients to be college educated, to have higher incomes, and dissatisfied with MD care. Compared with seekers of both GP and DC care, DC only patients in both countries have fewer chronic conditions, take fewer drugs, and have no regular doctor. U.S. DC only patients are more likely than GP+DC patients to be uninsured and dissatisfied with health care; Canadian DC only patients are more likely than GP+DC patients to be under 45, male, less educated, smokers, and not obese, without disabling back or neck pain, on fewer drugs, and lacking a regular doctor. CONCLUSION: Chiropractic and GP patients are dissimilar in both Canada and the U.S., with key differences between countries and between DC patients who do and do not seek care from GPs. Such variation has broad and potentially far-reaching health policy and research implications