Epidemiology of early-onset Parkinson's disease in Finland

Ylikotila, Pauli; Tiirikka, Timo; Moilanen, Jukka S.; Kääriäinen, Helena; Marttila, Reijo J.; Majamaa, Kari

doi:10.1016/j.parkreldis.2015.06.003

Cited by 28 publications

(29 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The quality scores of SERPINA1 variants were relatively low suggesting that this association may be a false positive finding. Notably, seven (25 %) out of the 28 cases with the rs141620200 variant had a positive family history with respect to PD, while a family history was reported by 45 cases (11 %) among the remaining EOPD patients (Ylikotila et al, 2015). Interestingly, a recent study including Finnish PD patients has suggested that certain serpinA1 isoforms differ between PD patients with or without dementia (Halbgebauer et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

“…We have previously ascertained a nationwide cohort of patients with early-onset PD (EOPD) (Ylikotila et al, 2015). In this cohort we have found that the birthplaces of patients with PD among first-degree relatives are clustered within the country and that the distance between the birthplaces of their parents was shorter than that among patients with negative family history.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study

Siitonen

Nalls

Hernandez

et al. 2017

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

Several genes and risk factors are associated with Parkinson’s disease (PD). Although many of the genetic markers belong to a common pathway, a unifying pathogenetic mechanism is yet to be found. Also, missing heritability analyses have estimated that only part of the genetic influence contributing to PD has been found. Here, we carried out whole-exome sequencing (WES) on 438 Finnish patients with early-onset PD. We also re-analyzed previous data from genome-wide association studies (GWAS) on the same cohort. Variants in the CEL gene/locus were associated with PD in both GWAS and WES analysis. Exome-wide gene-based association tests also identified the MPHOSPH10, TAS2R19 and SERPINA1 genes in the discovery dataset (p<2.5E-6). MPHOSPH10 had estimated odds ratio (OR) of 1.53 and the rs141620200 variant in SERPINA1 had OR of 1.27. We identified several candidate genes, but further investigation is required in order to determine the role of these genes in PD.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study

Siitonen

Nalls

Hernandez

et al. 2017

Neurobiology of Aging

Self Cite

View full text Add to dashboard Cite

show abstract

“…The study group consisted of a national cohort of 441 patients with EOPD defined by age of onset <55 years [9]. In addition, a case series collected at the Kuopio University Hospital during one year [10] comprised of 209 patients with late-onset Parkinson's disease (LOPD) and 55 patients with EOPD, and a case series collected at the Helsinki University Hospital [4] comprised 116 patients with LOPD and 31 patients with EOPD.…”

Section: Methodsmentioning

confidence: 99%

Genetic risk factors in Finnish patients with Parkinson's disease

Ylönen

Siitonen

Nalls

et al. 2017

Parkinsonism & Related Disorders

Self Cite

View full text Add to dashboard Cite

Introduction Variation contributing to the risk of Parkinson's disease (PD) has been identified in several genes and at several loci including GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT, but the frequencies of risk variants seem to vary according to ethnic background. Our aim was to analyze how variation in these genes contributes to PD in the Finnish population. Methods The subjects consisted of 527 Finnish patients with early-onset PD, 325 patients with late-onset PD and 403 population controls. We screened for known genetic risk variants in GBA, SMPD1, LRRK2, POLG1, CHCHD10 and MAPT. In addition, DNA from 225 patients with early-onset Parkinson's disease was subjected to whole exome sequencing (WES). Results We detected a significant difference in the length variation of the CAG repeat in POLG1 between patients with early-onset PD compared to controls. The p.N370S and p.L444P variants in GBA contributed to a relative risk of 3.8 in early-onset PD and 2.5 in late-onset PD. WES revealed five variants in LRRK2 and SMPD1 that were found in the patients but not in the Finnish ExAC sequences. These are possible risk variants that require further confirmation. The p.G2019S variant in LRRK2, common in North African Arabs and Ashkenazi Jews, was not detected in any of the 849 PD patients. Conclusions The POLG1 CAG repeat length variation and the GBA p.L444P variant are associated with PD in the Finnish population.

show abstract

“…Pramipexole patches containing different drug concentrations (3,6,10,15,20,25, and 30%, w/w) were prepared and stored at 40 ± 2°C, 75 ± 5% relative humidity in a temperature humidity chamber (Yongsheng Experiment Equipment Factory, Chongqing, China). Samples were withdrawn at 1, 2, 3, and 6 months and observed under an XSP-5 optical microscope (Shanghai Optical Instrument Factory, China).…”

Section: Rug Loading Capacity and Drug Stabilitymentioning

confidence: 99%

“…Parkinson's disease (PD) is the second most frequently occurring progressive neurodegenerative disorder, afflicting approximately 3% of the population over 60 years in age (1)(2)(3). PD patients suffer from symptoms of rigidity, bradykinesia, postural abnormalities, tremor at rest, and freezing (1).…”

Section: Introductionmentioning

confidence: 99%

Development of a Prolonged-Release Pramipexole Transdermal Patch: In Vitro and In Vivo Evaluation

Sun

et al. 2016

AAPS PharmSciTech

View full text Add to dashboard Cite

The current study aimed to develop a prolonged-release pramipexole (PPX) transdermal patch for the treatment of Parkinson's disease. Permeation parameters of PPX were investigated using human cadaver skin. Pramipexole patches were prepared using DURO-TAK pressure-sensitive-adhesive (PSA) and evaluated for drug stability, drug loading, in vitro drug release, and in vitro permeation through mouse skin. The results indicated that blends of DURO-TAK 87-2852 and DURO-TAK 87-2510 were suitable for creating a prolonged-release PPX patch due to their advantages in drug release, drug loading, and stability. The final formulation consisted of 87-2852/87-2510 (70:30), 10% PG, and 15% PPX and showed a cumulative permeation amount of 1497.19 ± 102.90 μg/cm with a continuous flux over 6.0 μg/(cm·h) across human cadaver skin for 7 days. In vivo studies in rats indicated that PPX patch produced a significantly longer (p < 0.001) half-life (t , 75.16 ± 17.37 h) and mean residence time (MRT, 135.89 ± 24.12 h) relative to oral tablets (Sifrol) and had a relative bioavailability of 51.64 ± 21.32%. Therefore, this study demonstrated the feasibility of developing a prolonged-release PPX patch, which proposed the potential to serve as an alternate to conventional oral tablets and may therefore improve patient compliance.

show abstract

Epidemiology of early-onset Parkinson's disease in Finland

Cited by 28 publications

References 25 publications

Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study

Genetics of early-onset Parkinson's disease in Finland: exome sequencing and genome-wide association study

Genetic risk factors in Finnish patients with Parkinson's disease

Development of a Prolonged-Release Pramipexole Transdermal Patch: In Vitro and In Vivo Evaluation

Contact Info

Product

Resources

About