Apolipoprotein E genotypes and the risk of Parkinson disease.
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ABSTRACT:
SUBMITTER: Gao J
PROVIDER: S-EPMC3172377 | biostudies-literature | 2011 Nov
REPOSITORIES: biostudies-literature
Publications
Apolipoprotein E genotypes and the risk of Parkinson disease.
Gao Jianjun J Huang Xuemei X Park Yikyung Y Liu Rui R Hollenbeck Albert A Schatzkin Arthur A Mailman Richard B RB Chen Honglei H
Neurobiology of aging 20110708 11
We examined apolipoprotein E (ApoE) genotypes in relation to Parkinson's disease (PD) among 786 cases and 1537 controls, all non-Hispanic Caucasians. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from multivariate logistic regression models, adjusting for year of birth, sex, smoking status, daily caffeine intake, and family history of PD. Compared with participants with ApoE ε33, ε4 carriers (ε34/ε44) had significantly lower odds for having PD (OR, 0.75; 95% CI, 0.59-0.94; p ...[more]
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Project description:To identify plasma-based biomarkers for Parkinson disease (PD) risk.In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity.One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.
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Project description:Few epidemiologic studies have evaluated the effects of air pollution on the risk of Parkinson disease (PD).We investigated the associations of long-term residential concentrations of ambient particulate matter (PM) < 10 ?m in diameter (PM10) and < 2.5 ?m in diameter (PM2.5) and nitrogen dioxide (NO2) in relation to PD risk.Our nested case-control analysis included 1,556 self-reported physician-diagnosed PD cases identified between 1995 and 2006 and 3,313 controls frequency-matched on age, sex, and race. We geocoded home addresses reported in 1995-1996 and estimated the average ambient concentrations of PM10, PM2.5, and NO2 using a national fine-scale geostatistical model incorporating roadway information and other geographic covariates. Air pollutant exposures were analyzed as both quintiles and continuous variables, adjusting for matching variables and potential confounders.We observed no statistically significant overall association between PM or NO2 exposures and PD risk. However, in preplanned subgroup analyses, a higher risk of PD was associated with higher exposure to PM10 (ORQ5 vs. Q1 = 1.65; 95% CI: 1.11, 2.45; p-trend = 0.02) among women, and with higher exposure to PM2.5 (ORQ5 vs. Q1 = 1.29; 95% CI: 0.94, 1.76; p-trend = 0.04) among never smokers. In post hoc analyses among female never smokers, both PM2.5 (ORQ5 vs. Q1 = 1.79; 95% CI: 1.01, 3.17; p-trend = 0.05) and PM10 (ORQ5 vs. Q1 = 2.34; 95% CI: 1.29, 4.26; p-trend = 0.01) showed positive associations with PD risk. Analyses based on continuous exposure variables generally showed similar but nonsignificant associations.Overall, we found limited evidence for an association between exposures to ambient PM10, PM2.5, or NO2 and PD risk. The suggestive evidence that exposures to PM2.5 and PM10 may increase PD risk among female never smokers warrants further investigation. Citation: Liu R, Young MT, Chen JC, Kaufman JD, Chen H. 2016. Ambient air pollution exposures and risk of Parkinson disease. Environ Health Perspect 124:1759-1765;?http://dx.doi.org/10.1289/EHP135.
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Project description:ImportanceParkinson disease (PD) is an increasingly common neurodegenerative disorder in many aging societies. Although comorbidities with mental disorders are common in PD, whether PD is associated with an increased risk of suicide is unclear.ObjectiveTo use a large national representative PD cohort to compare the risk of suicide in patients with PD and control participants and identify potential risk factors.Design, setting, and participantsThis nationwide population-based cohort study used linked data from Taiwan's National Health Insurance data set and Taiwan Death Registry between January 2002 and December 2016. Patients with incident PD diagnosed between January 2005 and December 2014 were followed up until December 2016. Four control participants from the general population were randomly selected by risk set sampling and were matched on age, sex, and residence to each affected individual. Data analysis occurred from June 2019 to October 2020.ExposuresDiagnosis of PD retrieved from the National Health Insurance data set.Main outcomes and measuresSuicide was recorded in the Taiwan Death Registry. Cox proportional models and hazard ratios (HRs) were used to estimate the association between PD and the risk of suicide over the follow-up period.ResultsOver 11 years, 35 891 patients with PD were followed up (17 482 women [48.7%]; mean [SD] age, 72.5 [10.1] years) and matched to 143 557 control participants (69 928 women [48.7%]; mean [SD] age, 72.5 [10.1] years). A total of 151 patients with PD (cumulative incidence, 66.6 per 100 000 [95% confidence limits [CL], 78.1-91.7]) and 300 control participants (cumulative incidence, 32.3 per 100 000 [95% CL, 36.2-40.5]) died by suicide. The risk of suicide was higher (HR, 2.1 [95% CL, 1.7-2.5]) in patients with PD than control participants, after adjustment for markers of socioeconomic position, medical comorbidities, and dementia. After controlling for mental disorders, the association between PD and suicide risk remained (HR, 1.9 [95% CL, 1.6-2.3]). Compared with control participants who died by suicide, those who died by suicide in the PD group were slightly younger (mean [SD] age: patients with PD, 74.0 [10.4] years vs control participants, 76.0 [10.2] years; P = .05) and more likely to be urban dwelling (medium urbanization, 39 patients with PD [25.8%] vs 115 control participants [38.3%]; high urbanization, 84 patients with PD [55.6%] vs 136 control participants [45.3%]; P = .03), have mental disorders (depression, 15 of 151 patients with PD [9.9%] vs 15 of 300 control participants [5.0%]; other mental disorders, 12 patients with PD [8.0%] vs 11 control participants [3.7%]; P = .02), and adopt jumping as a method of suicide (21 patients with PD [13.9%] vs 16 control participants [5.3%]; P < .01).Conclusions and relevanceIn this population-based cohort study, Parkinson disease, a common neurodegenerative disorder common in elderly persons, was independently associated with an increased risk of suicide. Integrating mental health care into primary care and PD specialty care, along with socioenvironmental interventions, may help decrease the risk of suicide in patients with PD.
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Project description:BackgroundNeuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies.MethodsWe prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations.ResultsWe identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42-0.93; p = 0.02). There was a dose-response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78-1.26), other NSAIDs (RR = 1.26; 95% CI 0.86-1.84), or acetaminophen (RR = 0.86; 95% CI 0.62-1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63-0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk.ConclusionsThe association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD.
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