Introduction: There has been a bias in the existing literature on Parkinson’s disease (PD) genetics as most studies involved patients of European ancestry, mostly in Europe and North America. Our ...target was to review published research data on the genetic profile of PD patients of non-European or mixed ancestry. Methods: We reviewed articles published during the 2000–2023 period, focusing on the genetic status of PD patients of non-European origin (Indian, East and Central Asian, Latin American, sub-Saharan African and Pacific islands). Results: There were substantial differences regarding monogenic PD forms between patients of European and non-European ancestry. The G2019S Leucine Rich Repeat Kinase 2 (LRRK2) mutation was rather scarce in non-European populations. In contrast, East Asian patients carried different mutations like p.I2020T, which is common in Japan. Parkin (PRKN) variants had a global distribution, being common in early-onset PD in Indians, in East Asians, and in early-onset Mexicans. Furthermore, they were occasionally present in Black African PD patients. PTEN-induced kinase 1 (PINK1) and PD protein 7 (DJ-1) variants were described in Indian, East Asian and Pacific Islands populations. Glucocerebrosidase gene variants (GBA1), which represent an important predisposing factor for PD, were found in East and Southeast Asian and Indian populations. Different GBA1 variants have been reported in Black African populations and Latin Americans. Conclusions: Existing data reveal a pronounced heterogeneity in the genetic background of PD. A number of common variants in populations of European ancestry appeared to be absent or scarce in patients of diverse ethnic backgrounds. Large-scale studies that include genetic screening in African, Asian or Latin American populations are underway. The outcomes of such efforts will facilitate further clinical studies and will possibly contribute to the identification of either new pathogenic mutations in already described genes or novel PD-related genes.
Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this ...relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes.
Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history.
In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%).
We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.
the apolipoprotein e4 allele (
) constitutes an established genetic risk factor for Alzheimer's Disease Dementia (ADD). We aimed to explore the frequency of the
isoforms in the Greek population of ...Southern Greece.
peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche's Light Cycler PCR platform.
allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group.
homozygosity was the most common genotype, while the frequency of
homozygosity was higher in the AD group (8.60%).
carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: 1.90-10.61 and OR: 3.82, 95% CI: 1.59-9.17, respectively).
this study examines the
isoforms and is the first to report a higher
frequency in MCI compared with healthy controls in southern Greece. Importantly, we report the occurrence of the
allele, related to ADD, as amongst the lowest globally reported, even within the nation, thus enhancing the theory of ethnicity and latitude contribution.
•Erythrocyte membrane α-syn dimer is elevated in PD patients with no known mutations.•Erythrocyte membrane α-syn dimer is elevated in PD patients with GBA mutations.•There is no α-syn dimer level ...difference in p.A53T α-syn mutation carriers.•The increased α-synuclein dimer levels may be due to altered lipid composition of the erythrocyte membrane.
Variations of α-synuclein levels or species have been reported in Parkinson’s Disease (PD). There has been little systematic examination of erythrocytes, a rich source of α-synuclein.
Erythrocyte membranes were obtained from PD patients (mutation carriers in the α-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n=18 each), and patients without known mutations (GU-PD, n=56)), and age-/sex-matched controls (n=56). Levels of monomeric and dimeric α-synuclein were assessed using Western immunoblotting.
A statistically significant increase of α-synuclein dimer and dimer to monomer ratio was found in GBA-PD and GU-PD. In contrast, dimer levels of A53T-PD were not different from controls. No difference was found in α-synuclein monomer levels.
The increased α-synuclein dimer in GBA-PD and GU-PD is suggestive of an apparent systemic dysfunction causing the dimerization, and potentially oligomerization, of α-synuclein. These results may have implications for PD pathogenesis and biomarker development.
Age at onset is one of the most critical factors contributing to the clinical heterogeneity of Parkinson's disease (PD), and available evidence is rather conflicting.
The aim of this study is to ...investigate the clinical differences between early-onset PD (EOPD) and mid-and-late-onset PD (MLOPD) in the Greek population, based on the existing data of the Hellenic Biobank of PD (HBPD).
HBPD contains information of PD cases from two centers in Greece during 2006–2017. Patients with the A53T mutation in the SNCA gene or mutations in the GBA1 gene were excluded. Associations between clinical characteristics (motor and non-motor symptoms, side of onset, first symptom, motor complications) and MLOPD versus EOPD were explored with a single logistic regression model adjusting for gender, family history of PD, disease and dopaminergic therapy duration, disease severity (UPDRS III), levodopa equivalent daily dose, as well as each of the other clinical characteristics.
675 patients (129 EOPD, 546 MLOPD) were included. EOPD was more frequently associated with dystonia (OR 0.19, 95% CI 0.08–0.50, p < 0.01) and motor complications (0.23, 0.07–0.76, 0.02), compared to MLOPD. Bilateral onset (9.38, 1.05–84.04, 0.045) and autonomic dysfunction (2.31, 1.04–5.11, 0.04) were more frequently associated with MLOPD.
EOPD and MLOPD display distinct clinical profiles, regarding motor and non-motor symptoms, side of onset and motor complications in the Greek population. These differences may reflect diverse pathophysiological backgrounds, potentially attributed to genetic or age-related epigenetic influences.
•Evidence of early-onset PD (EOPD) vs mid-and-late-onset (MLOPD) in Greece is scant.•50 years of age at onset is the usual cut-off point for EOPD.•EOPD is more frequently associated with dystonia and motor complications.•Bilateral onset and autonomic dysfunction are more frequently associated with MLOPD.•These differences shed more light on understanding EOPD vs MLOPD pathophysiology.
The aim of this study is to investigate the association between environmental factors (smoking, coffee, pesticide exposure) and Parkinson's disease (PD) subtypes (early-onset, mid-and-late onset, ...familial and sporadic) in the Greek population.
The Hellenic Biobank of PD recorded information of PD cases and controls from two centers in Greece during 2006–2017. Patients with the A53T mutation in SNCA or GBA mutations were excluded. Associations of environmental factors with PD overall (and PD subtypes) versus controls were explored with logistic regression models adjusting for age, gender and each environmental factor.
686 patients and 356 controls were included. Smoking was associated with a reduced risk of PD overall (OR 0.48, 95% CI 0.35–0.67), mid-and-late onset (0.46, 0.32–0.66), familial (0.53, 0.34–0.83) and sporadic (0.46, 0.32–0.65), but not early-onset PD. There was an inverse linear association with pack-years of smoking, except for early-onset PD. Early-onset PD was the only PD subtype inversely associated with coffee consumption when dichotomously treated. Compared to never-coffee drinkers, only those at the upper tertile had lower odds for PD overall (0.52, 0.29–0.91), early-onset (0.16, 0.05–0.53) and familial PD (0.36, 0.17–0.75). No associations were found between pesticides and PD.
Our study shows that the well-known negative association of smoking with PD occurs across all PD subtypes in the Greek population, apart from early-onset PD. Early-onset PD was also most strongly inversely associated with coffee consumption, highlighting a potential distinct underlying physiopathology in this PD subset that may involve specific gene-environment interactions.
•Smoking is inversely associated with mid-late but not early-onset PD.•Smoking is inversely associated with both familial and sporadic PD.•Smoking pack-years are inversely linearly associated with PD.•Heavy coffee intake is inversely associated with PD overall.•Heavy coffee intake is inversely associated only with early-onset and familial PD subtypes.
