Epidemiology, environmental risk factors and genetics of Parkinson's disease

doi:10.1016/j.lpm.2017.01.001

La Presse Médicale

Volume 46, Issue 2, Part 1, March 2017, Pages 175-181

https://doi.org/10.1016/j.lpm.2017.01.001 Get rights and content

Key points

Parkinson's disease (PD) is a frequent neurodegenerative disease with a premotor phase that lasts several years.

Risk factors that have been linked to PD are tobacco, caffeine, black tea, pesticides and calcium channel blockers.

Some risk factors may be due to inverse causality (e.g. changes in personality during the premotor phase).

The genetics of PD are complex with a contribution of Mendelian (e.g. SNCA, LRRK2, Parkin, Pink1,…) and non-Mendelian factors (e.g. single nucleotide polymorphisms).

Glucocerebrosidase gene mutations (Gaucher disease) are currently the strongest genetic risk factor for PD.

Studying risk factors will help to better understand the pathogenesis of PD.

Points essentiels

La maladie de Parkinson est une maladie neurodégénérative fréquente dont la phase pré-motrice est longue de plusieurs années.

Plusieurs facteurs de risque ont été rapportés comme le tabac, la caféine, le thé noir, les pesticides et les inhibiteurs des canaux calciques.

Certaines associations entre la maladie de Parkinson et ses facteurs de risque peuvent être expliquées par une relation de causalité inverse (par exemple des changements de personnalité pendant la phase pré-motrice)

Les bases génétiques de la maladie de Parkison sont complexes, impliquant des transmissions mendéliennes (par exemple SNCA, LRRK2, Parkin, Pink1,…) et non mendéliennes (comme les polymorphismes nucléotidiques).

Les mutations du gène de la glucocérébrosidase, responsables de la maladie de Gaucher, sont le facteur de risque le plus élevé de la maladie de Parkinson.

Étudier ses facteurs de risques permet de mieux comprendre la physiopathologie de la maladie de Parkinson.

Introduction

Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease. Since ageing is the most important risk factor, the prevalence is expected to increase over the next decades. Several environmental and genetic factors conferring an increased risk for PD have been identified in recent years. These risk factors will be reviewed below. Inverse causality may account for some of them since the long premotor phase of PD may influence the patient's habits or personality and thus the exposure to environmental risk factors.

Section snippets

Epidemiology

Many studies have focused on the epidemiology of PD and related disorders. The incidence and prevalence vary with methodology of the studies and populations targeted. A recent meta-analysis confirmed an age-dependent prevalence, ranging between 41 per 100,000 inhabitants between 40 and 49 years and 1903 per 100,000 inhabitants older than 80. Men are more affected than women, especially in the 50–59-year-old group where the prevalence is 134 men and 41 women per 100,000 individuals. In the

Cigarette smoking

Numerous studies have focused on the inverse correlation between cigarette smoking and PD risk. In meta-analyses, smoking was protective against PD, with pooled odds ratios ranging from 0.23 to 0.70 [3], [4]. An inverse correlation was reported between the number of cigarettes per day, the number of years of smoking, the number of pack-years and the risk for PD, as well as a correlation between the number of years since quitting and the risk for PD. Depending on the studies, this effect

Genetics of PD

Numerous studies have focused on the genetics of PD. Over the last two decades, several genes causing monogenic familial forms of PD have been identified (table I). More recently, in genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) of several genes, including the SNCA gene that codes for alpha-synuclein were found to be associated with an increased risk for PD [42]. Studying these genes may help to better understand the molecular processes underlying the

Conclusion

PD is a complex disease with both environmental and genetic contributors. Studying these risks factors will help to better understand underlying disease mechanisms and phenotypical heterogeneity. It is now established that PD starts many years before the onset of classical motor signs. Accordingly, changes in personality or habits occurring during the preclinical or premotor period may precede the diagnosis and influence the exposition to numerous environmental factors (e.g. alcohol, tobacco,

Disclosure of interest

the authors declare that they have no competing interest.

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Our recent study revealed that fluorescent lamp light can penetrate deep into the brain of mice and rats leading to the development of typical histological characteristics associated with Parkinson’s disease such as the loss of dopamine neurons in the substantia nigra. Monochromatic LED lights were thus used in this work to deepen our knowledge on the effects of the major wavelength peaks of fluorescent light on mouse and human dopaminergic cells. In particular, we exposed immortalized dopaminergic MN9D neuronal cells, primary cultures of mouse mesencephalic dopaminergic cells and human dopaminergic neurons differentiated from induced pluripotent stem cells (hiPSC) to different LED light wavelengths. We found that chronic exposure to LED light reduced overall undifferentiated MN9D cell number, with the most significant effects observed at wavelengths of 485 nm and 610 nm. Moreover, LED light especially at 610 nm was able to negatively impact on the survival of mouse mesencephalic dopaminergic cells and of human dopaminergic neurons derived from hiPSC. Notably, differentiated MN9D dopaminergic cells, which closely resemble mature dopamine neuronal phenotype, acutely exposed for 3 h at 610 nm, showed a clear increase in ROS production and cytotoxicity compared to controls undifferentiated MN9D cells. These increases were even more pronounced by the co-treatment with the oxidative agent H₂O₂. Collectively, these findings suggest that specific wavelengths, particularly those capable of penetrating deep into the brain, could potentially pose an environmental hazard in relation to Parkinson's disease.
MicroRNA-217-5p triggers dopaminergic neuronal degeneration via autophagy activation under Atrazine exposure
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Atrazine (ATR) is a widely used agricultural herbicide, and its accumulation in soil and water can cause various environmental health problems. ATR has neurotoxic effects on dopaminergic neurons, which can lead to a Parkinson's disease (PD)-like syndrome. Epigenetics regulates gene expression dynamically through DNA methylation, histone post-translational modification, microRNA (miRNA) interaction, and RNA methylation. MicroRNA (miRNA), representing one of the primary epigenetic mechanisms responsible for regulating gene expression, plays a crucial role in maintaining normal cellular function, while dysregulation of miRNA expression has been observed in PD. This study aims to investigate the regulatory mechanisms of miRNA in ATR exposure. The results show that ATR-exposure significantly upregulates the expression level of miR-217-5p. Both miR-217-5p overexpression and ATR exposure is able to trigger the autophagy process and apoptosis. Conversely, inhibiting the expression of miR-217-5p can reverse the levels of ATR-induced autophagy and apoptosis. Moreover, ATR causes damage to dopaminergic neurons, as indicated by the altered expression of tyrosine hydroxylase and α-synuclein. Taken together, these results suggest that ATR-induced autophagy can accelerate the progression of neurodegenerative diseases and that miR-217-5p is probably an important target involved in ATR-induced dopaminergic damage, shedding important light on the development of a novel strategy for treating neurodegenerative diseases.
Caffeine intake interacts with Asian gene variants in Parkinson's disease: a study in 4488 subjects
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Caffeine intake reduces risk of Parkinson's disease (PD), but the interaction with genes is unclear. The interaction of caffeine with genetic variants in those at high PD risk has healthcare importance. We investigate interactions of caffeine intake with risk variants found in Asians, and determine PD risk estimates in caffeine-drinkers carrying these variants.
PD patients and controls without neurological disorders were included. Caffeine intake was assessed using a validated evaluation tool. Leucine rich repeat kinase 2 (LRRK2) risk variants were genotyped. Statistical analysis was conducted with logistic regression models. Gene-caffeine interactions were quantified using attributable proportion (AP) due to interaction (positive interaction defined as AP >0).
5100 subjects were screened and 4488 subjects (1790 PD, 2698 controls) with genetic data of at least one LRRK2 variant were included. Risk-variant-carriers who were non-caffeine-drinkers had increased PD odds compared to wildtype carriers who were caffeine-drinkers for G2385R [OR 8.6 (2.6–28.1) p < 0.001; AP = 0.71], R1628P [OR 4.6 (1.6–12.8) p = 0.004; AP = 0.50] and S1647T [OR 4.0 (2.0–8.1) p < 0.001; AP = 0.55] variants.
Caffeine intake interacts with LRRK2 risk variants across three different groups of gene carriers. Asymptomatic risk-variant-carriers who are non-caffeine-drinkers have four to eight times greater PD risk compared to wildtype-caffeine-drinkers. Lifestyle modifications to mitigate PD risk in asymptomatic healthy risk variant carriers have potential roles in our Asian cohort.
This study was supported by the National Medical Research Council (STaR and PD OF LCG 000207 grants) and Duke-NUS Medical School.
Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China
2023, Neuroscience Letters
The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction.
This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population.
This study enrolled 351 patients with sporadic PD and 240 normal controls in Chinese Han population. Peripheral blood DNA was extracted by DNA extraction kits and the rs1423099 genotype was analyzed by Agena MassARRAY DNA mass spectrometry. The differences in genotype and allele distribution frequencies between PD patients and control groups were compared using chi-squared tests or Fisher's exact tests.
No statistical difference was revealed in age and sex distribution between the cases and control groups, and the distribution of genotype and allele frequencies was consistent with the Hardy-Weinberg equilibrium test. In SV2C rs1423099 dominant model, the frequency of the CC/CT genotype was significantly higher in the PD group compared to the control group (OR = 4.065,95% CI: 2.801–10.870, p = 0.002). Nevertheless, in the recessive model, CC or CT/TT genotypes have no statistical difference in the two groups (p = 0.09). Additionally, in allelic analysis, the C allele was investigated to increase the risk of PD (OR = 1.346, 95% CI: 1.036–1.745, p = 0.026); Furthermore, subgroup analysis suggested that those carrying the C allele in the male subgroup were at a higher risk to afflicted with PD (OR = 1.637, 95% CI: 1.147–2.336, p = 0.006).
SV2C rs1423099 single nucleotide polymorphism was associated with sporadic Parkinson's disease in the Chinese Han population, particularly in males.
Efficacy of invasive and non-invasive methods for the treatment of Parkinson's disease: Nanodelivery and enriched environment
2023, International Review of Neurobiology
Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta and the subsequent motor disability. The most frequently used treatments in clinics, such as L-DOPA, restore dopaminergic neurotransmission in the brain. However, these treatments are only symptomatic, have temporary efficacy, and produce side effects. Part of the side effects are related to the route of administration as the consumption of oral tablets leads to unspecific pulsatile activation of dopaminergic receptors. For this reason, it is necessary to not only find alternative treatments, but also to develop new administration systems with better security profiles. Nanoparticle delivery systems are new administration forms designed to reach the pharmacological target in a highly specific way, leading to better drug bioavailability, efficacy and safety. Some of these delivery systems have shown promising results in animal models of PD not only when dopaminergic drugs are administered, but even more when neurotrophic factors are released. These latter compounds promote maturation and survival of dopaminergic neurons and can be exogenously administered in the form of pharmacological therapy or endogenously generated by non-pharmacological methods. In this sense, experimental exposure to enriched environments, a non-invasive strategy based on the combination of social and inanimate stimuli, enhances the production of neurotrophic factors and produces a neuroprotective effect in parkinsonian animals. In this review, we will discuss new nanodelivery systems in PD with a special focus on therapies that increase the release of neurotrophic factors.
Lipid profile in Parkinson's disease: The potential role of brain-derived neurotrophic factor
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Parkinson's disease is a neurodegenerative disease manifested as increased tremor, bradykinesia, rigidity, and postural instability. Brain-derived neurotrophic factor (BDNF) is essential for neurocognitive function. However, its cardiometabolic effect has recently been identified in health and disease, but not in PD. Therefore, the current study examined the relationship of BDNF with glucose and lipid profile.
This was a cross sectional comparative study where PD patients (n = 26) and age-matched healthy controls (n = 27) were recruited. Blood samples were drawn to determine BDNF, glucose, and lipid profile including total cholesterol (TC), HDL, LDL, triglyceride (TriG).
The linear regression showed that BDNF predicted 11.9 % of TC (p = 0.05), 3.0 % of HDL (p = 0.003), 27.3 % of LDL (p = 0.006), 16.6 % of TriG (p = 0.04), 15.8 % of TC/HDL (p = 0.06), 22.1 % of TC/LDL (p = 0.01), and 35.1 % of TriG/HDL (p = 0.001) but not glucose (B = -0.006; CI = -0.19/0.18; F = 0.005; p = 0.9) and LDL/HDL (B = 0.06; CI = -0.17/0.3; F = 0.3; p = 0.6). Subsequent ANCOVA revealed differences (p < 0.05) in TC, HDL, LDL, TC/LDL, and TriG/HDL but not in glucose, TriG, and TC/HDL among the patients with low-BDNF versus high-BDNF.
The results demonstrate a relationship of BDNF with lipid profile suggesting the importance of BDNF for lipid metabolism in PD.

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UpdateEpidemiology, environmental risk factors and genetics of Parkinson's diseaseÉpidémiologie, facteurs de risque environnementaux et génétiques de la maladie de Parkinson

Key points

Points essentiels

Introduction

Section snippets

Epidemiology

Cigarette smoking

Genetics of PD

Conclusion

Disclosure of interest

Environ Int

Parkinsonism Relat Disord

Clin Neurol Neurosurg

Lancet

Lancet

Parkinsonism Relat Disord

Mol Cell Neurosci

The prevalence of Parkinson's disease: a systematic review and meta-analysis

Mov Disord

The incidence of Parkinson's disease: a systematic review and meta-analysis

Neuroepidemiology

Pooled analysis of tobacco use and risk of Parkinson disease

Arch Neurol

Association between Parkinson's disease and cigarette smoking, rural living, well-water consumption, farming and pesticide use: systematic review and meta-analysis

PLoS One

Risk factors for neurodegeneration in idiopathic rapid eye movement sleep behavior disorder: a multicenter study

Ann Neurol

Caffeine exposure and the risk of Parkinson's disease: a systematic review and meta-analysis of observational studies

J Alzheimers Dis

Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease

J Neurosci

Differential effects of black versus green tea on risk of Parkinson's disease in the Singapore Chinese Health Study

Am J Epidemiol

Professional exposure to pesticides and Parkinson disease

Ann Neurol

Interaction between ABCB1 and professional exposure to organochlorine insecticides in Parkinson disease

Arch Neurol

Diabetes and risk of Parkinson's disease: a systematic review and meta-analysis

Diabetes Care

Diabetes and risk of Parkinson's disease: an updated meta-analysis of case-control studies

PLoS One

Risk of Parkinson disease in diabetes mellitus: an updated meta-analysis of population-based cohort studies

Medicine (Baltimore)

Glitazone treatment and incidence of parkinson's Disease among people with diabetes: a retrospective cohort study

PLoS Med

Reduced incidence of Parkinson's disease after dipeptidyl peptidase-4 inhibitors – A nationwide case-control study

Mov Disord

Pioglitazone in early Parkinson's disease: a phase 2, multicentre, double-blind, randomised trial

Lancet Neurol

Body mass index and risk of Parkinson's disease: a dose-response meta-analysis of prospective studies

PLoS One

Total cholesterol and the risk of Parkinson disease

Neurology

Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation

PLoS Genet

Serum cholesterol levels and the risk of Parkinson's disease

Am J Epidemiol

Statin use and the risk of Parkinson's disease: an updated meta-analysis

PLoS One

Statin use and the risk of Parkinson disease

Neurology

Update
Epidemiology, environmental risk factors and genetics of Parkinson's diseaseÉpidémiologie, facteurs de risque environnementaux et génétiques de la maladie de Parkinson