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ABSTRACT: BACKGROUND: We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. METHODS: From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. RESULTS: The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). CONCLUSIONS: Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures.
Environment international 04/2013; 56C:42-47. · 4.79 Impact Factor
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ABSTRACT: OBJECTIVES: Traumatic brain injury (TBI) increased risk of Parkinson disease (PD) in many but not all epidemiologic studies, giving rise to speculations about modifying factors. A recent animal study suggested that the combination of TBI with subthreshold paraquat exposure increases dopaminergic neurodegeneration. The objective of our study was to investigate PD risk due to both TBI and paraquat exposure in humans. METHODS: From 2001 to 2011, we enrolled 357 incident idiopathic PD cases and 754 population controls in central California. Study participants were asked to report all head injuries with loss of consciousness for >5 minutes. Paraquat exposure was assessed via a validated geographic information system (GIS) based on records of pesticide applications to agricultural crops in California since 1974. This GIS tool assesses ambient pesticide exposure within 500 m of residences and workplaces. RESULTS: In logistic regression analyses, we observed a 2-fold increase in risk of PD for subjects who reported a TBI (adjusted odds ratio [AOR] 2.00, 95% confidence interval [CI] 1.28-3.14) and a weaker association for paraquat exposures (AOR 1.36, 95% CI 1.02-1.81). However, the risk of developing PD was 3-fold higher (AOR 3.01, 95% CI 1.51-6.01) in study participants with a TBI and exposure to paraquat than those exposed to neither risk factor. CONCLUSIONS: While TBI and paraquat exposure each increase the risk of PD moderately, exposure to both factors almost tripled PD risk. These environmental factors seem to act together to increase PD risk in a more than additive manner.
Neurology 11/2012; 79(20):2061-2066. · 8.31 Impact Factor
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ABSTRACT: Maternal exposure to ambient air pollution has been associated with adverse birth outcomes such as preterm delivery. However, only one study to date has linked air pollution to blood pressure changes during pregnancy, a period of dramatic cardiovascular function changes. Objectives: We examined whether maternal exposures to criteria air pollutants, including particles of less than 10 μm (PM(10)) or 2.5 μm diameter (PM(2.5)), carbon monoxide (CO), nitrogen dioxide (NO(2)), sulfur dioxide (SO(2)), and ozone (O(3)), in each trimester of pregnancy are associated with magnitude of rise of blood pressure between the first 20 weeks of gestation and late pregnancy in a prospectively followed cohort of 1684 pregnant women in Allegheny County, PA.
Air pollution measures for maternal ZIP code areas were derived using Kriging interpolation. Using logistic regression analysis, we evaluated the associations between air pollution exposures and blood pressure changes between the first 20 weeks of gestation and late pregnancy.
First trimester PM(10) and ozone exposures were associated with blood pressure changes between the first 20 weeks of gestation and late pregnancy, most strongly in non-smokers. Per interquartile increases in first trimester PM(10) and O(3) concentrations were associated with mean increases in systolic blood pressure of 1.88 mm Hg (95% CI=0.84 to 2.93) and 1.84 (95% CI=1.05 to 4.63), respectively, and in diastolic blood pressure of 0.63 mm Hg (95% CI=-0.50 to 1.76) and 1.13 (95% CI=-0.46 to 2.71) in non-smokers.
Our novel finding suggests that first trimester PM(10) and O(3) air pollution exposures increase blood pressure in the later stages of pregnancy. These changes may play a role in mediating the relationships between air pollution and adverse birth outcomes.
Environmental Research 07/2012; 117:46-53. · 3.40 Impact Factor
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ABSTRACT: Despite numerous studies of air pollution and adverse birth outcomes, few studies have investigated preeclampsia and gestational hypertension, two pregnancy disorders with serious consequences for both mother and infant. Relying on hospital birth records, we conducted a cohort study identifying 34,705 singleton births delivered at Magee-Women's Hospital in Pittsburgh, PA between 1997 and 2002. Particle (<10 μm-PM(10); <2.5 μm-PM(2.5)) and ozone (O(3)) exposure concentrations in the first trimester of pregnancy were estimated using the space-time ordinary Kriging interpolation method. We employed multiple logistic regression estimate associations between first trimester exposures and preeclampsia, gestational hypertension, preterm delivery, and small for gestational age (SGA) infants. PM(2.5) and O(3) exposures were associated with preeclampsia (adjusted OR = 1.15, 95 % CI = 0.96-1.39 per 4.0 μg/m(3) increase in PM(2.5); adjusted OR = 1.12, 95 % CI = 0.89-1.42 per 16.8 ppb increase in O(3)), gestational hypertension (for PM(2.5) OR = 1.11, 95 % CI = 1.00-1.23; for O(3) OR = 1.12, 95 % CI = 0.97-1.29), and preterm delivery (for PM(2.5) ORs = 1.10, 95 % CI = 1.01-1.20; for O(3) ORs = 1.23, 95 % CI = 1.01-1.50). Smaller 5-8 % increases in risk were also observed for PM(10) with gestational hypertension and SGA, but not preeclampsia. Our data suggest that first trimester exposure to particles, mostly PM(2.5), and ozone, may increase the risk of developing preeclampsia and gestational hypertension, as well as preterm delivery and SGA.
Maternal and Child Health Journal 04/2012; · 2.24 Impact Factor
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ABSTRACT: It is not well understood how air pollution leads to adverse pregnancy outcomes. One pathway may be through C-reactive protein, a biomarker of systemic inflammation that has been reported to increase the risk of preterm delivery. We examined whether air pollution influences serum concentrations of C-reactive protein in early pregnancy.
We studied 1696 pregnant women in Allegheny County, PA, from 1997 through 2001. C-reactive protein concentrations were assayed in blood collected before the 22nd week of gestation. We estimated levels of particles of less than 10 μm (PM10) and less than 2.5 μm diameter (PM2.5), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone at the maternal zip code using Kriging interpolation for measurements obtained from ambient stations. Associations between air pollution and high C-reactive protein concentrations (≥ 8 ng/mL) were evaluated using logistic regression.
Among nonsmokers, an observed 9.2 μg/m increase in PM10 (averaged over 28 days prior to the blood sample) was associated with an odds ratios of 1.41 for high C-reactive protein concentrations (95% confidence interval = 0.99-2.00). Similarly, a 4.6 μg/m increase in PM2.5 was associated with an odds ratio of 1.47 (1.05-2.06). The odds ratio was 1.49 (0.75-2.96) per 7.9 ppb increase in ozone during summer. There were no associations in smokers or for other air pollutants, and there was no evidence for effect-measure modification by obesity.
PM10, PM2.5, and ozone exposures were associated with increased C-reactive protein concentrations in early pregnancy, suggesting that these air pollutants contribute to inflammation and thereby possibly to adverse pregnancy outcomes.
Epidemiology (Cambridge, Mass.) 07/2011; 22(4):524-31. · 5.51 Impact Factor
