scholarly journals The Association between E326K of GBA and the Risk of Parkinson’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yongpan Huang ◽  
Langmei Deng ◽  
Yanjun Zhong ◽  
Minhan Yi

It is reported that both the homozygous and heterozygous states of GBA mutations which are the causes of Gaucher disease (GD) are linked to the risk of PD. However, the GBA variant p.E326K (c.1093G > A, rs2230288), which does not result in GD in homozygous carriers, has triggered debate among experts studying Parkinson's disease (PD). In order to determine if the E326K variant of GBA is associated with the risk of PD, a standard meta-analysis was conducted by searching and screening publications, data extraction, and statistical analysis. Finally, a total of 15 publications, containing 5,908 PD patients and 5,605 controls, were included in this analysis. The pooled OR of the E326K genotype analysis was 1.99 (95% CI: 1.57–2.51). The minor allele frequencies of E326K for PD patients and controls were 1.67% and 1.03%, respectively. The pooled OR for the minor allele A was 1.99 (95% CI: 1.58–2.50). According to the subgroup analysis, we found that the significant differences between PD patients and controls for both genotype and allele of E326K also exist in Asians and Caucasians, respectively. In this study, we found that E326K of GBA is associated with the risk of PD in total populations, Asians, and Caucasians, respectively. Further studies are needed to clarify the role of GBA in the pathogenesis of PD.

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 674
Author(s):  
Han-Lin Chiang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Chiung-Mei Chen

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3′ untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = −3.96; p < 0.0001) and the dominant models (Z = −4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1751 ◽  
Author(s):  
Lucy M Collins ◽  
Janelle Drouin-Ouellet ◽  
Wei-Li Kuan ◽  
Timothy Cox ◽  
Roger A Barker

Background: Recently, the development of Parkinson’s disease (PD) has been linked to a number of genetic risk factors, of which the most common is glucocerebrosidase (GBA) mutations. Methods: We investigated PD and Gaucher Disease (GD) patient derived skin fibroblasts using biochemistry assays. Results: PD patient derived skin fibroblasts have normal glucocerebrosidase (GCase) activity, whilst patients with PD and GBA mutations have a selective deficit in GCase enzyme activity and impaired autophagic flux. Conclusions: This data suggests that only PD patients with a GBA mutation have altered GCase activity and autophagy, which may explain their more rapid clinical progression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaocui Qin ◽  
Xia Zhang ◽  
Pinyu Li ◽  
Min Wang ◽  
Li Yan ◽  
...  

Background: Diabetes mellitus (DM) increases the risk of Parkinson's disease (PD). However, whether DM medications play a part on that increased PD risk is unclear. We designed this meta-analysis to assess the influence of different oral DM medications on the PD risk in patients with DM.Methods: We searched PubMed, Embase, and CENTRAL databases for relevant studies up until January 2021. We pooled adjusted outcomes to assess the PD risk in patients using different DM medications including sulfonylurea, metformin, glitazones (GTZ), dipeptidyl peptidase-4 inhibitors (DPP4i), and glucagon-like peptide-1 agonists (GLP1a).Results: We included 10 studies in our analysis. Our results indicate a lack of significant association between the PD risk and the use of sulfonylureas (three studies; HR, 1.26; 95% CI, 0.95 to 1.66; I2, 70%; p = 0.11), DPP4i (three studies; HR, 0.69; 95% CI, 0.35 to 1.38; I2, 88%; p = 0.30), metformin (five studies; HR, 1.23; 95% CI, 0.98 to 1.78; I2, 84%; p = 0.13), and GTZ (six studies; HR, 0.88; 95% CI, 0.66 to 1.16; I2, 92%; p = 0.35). After exclusion of a single study in the GTZ analysis, our results indicate a significantly reduced PD risk with GTZ use (HR, 0.78; 95% CI, 0.65 to 0.93; I2, 59%; p = 0.06). Similarly, after the exclusion of a single study, our results indicate a significantly increased PD risk with the use of metformin (HR, 1.50; 95% CI, 1.11 to 2.02; I2, 80%; p = 0.008). We also found a significantly reduced PD risk with the use of GLP1a (two studies; HR, 0.41; 95% CI, 0.19 to 0.87; I2, 0%; p = 0.02).Conclusion: The role of different DM medications on the PD risk remains unclear, and the quality of studies is low. While our analysis suggests a lack of association between the use of metformin, GTZ, DPP4i, and sulfonylureas and the PD risk, metformin (to a higher degree) and GTZ may still increase the risk. Limited data suggest a protective effect of GLP1a on the PD risk.


2015 ◽  
Vol 18 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Stefania Mariani ◽  
Mariacarla Ventriglia ◽  
Illaria Simonelli ◽  
Serena Bucossi ◽  
Mariacristina Siotto ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Kui Chen ◽  
Yan Tan ◽  
You Lu ◽  
Jiayan Wu ◽  
Xueyuan Liu ◽  
...  

Background. Exercise has an integral impact on the physical and mental wellbeing of patients with Parkinson’s disease (PD), yet no comprehensive and quantitative analysis has been conducted on the effect of exercise on quality of life (QoL) in these patients. This study aimed to evaluate the effect of exercise on overall QoL and different domains of QoL in people with PD, as well as investigating the influence of factors such as the exercise type and intervention period. Methods. Databases, such as PubMed, Embase, and Cochrane Central Register of Controlled Trials, were searched since inception to August 14, 2018 to identify randomized controlled trials that compare the effect of exercise versus no intervention on QoL in PD patients. Following the subgroup analysis, heterogeneity was further explored. The quality of eligible studies was assessed according to PRISMA guidelines. Results. 20 studies were included with 1,143 participants in total. A meta-analysis showed a significant improvement in QoL after exercise intervention in PD patients (SMD = −0.24, 95% CI = −0.36 to −0.12, P<0.001). A subgroup analysis of exercise types revealed significant QoL improvement with aerobic exercise, martial arts, and dance, but not anaerobic exercise and combined exercise. Interventions lasting 12 weeks or longer improved QoL significantly. Conclusions. Exercise interventions, especially aerobic exercise, dance, and Tai Chi, significantly improve QoL in PD patients. At least 12 weeks of exercise is needed to bring about significant benefits.


2013 ◽  
Vol 19 (10) ◽  
pp. 1109-1118 ◽  
Author(s):  
Siddharth Ramanan ◽  
Devvarta Kumar

AbstractProspective memory (PM) refers to the ability to remember to carry out an intended action in the future and it is pervasive in our daily living. A failure to execute an intended action (e.g., take medication) at the appropriate juncture in future (e.g., after dinner) can negatively affect our daily functioning and at times, may have devastating effects (e.g., forgetting to turn off the gas stove before leaving the house). Patients with Parkinson's disease (PD) exhibit widespread cognitive deficits including deficits in PM. The present study provides a meta-analytic review of PM in PD. Results across nine studies indicated time and event-based PM to be similarly impaired in PD, with time-based PM compromised to a slightly larger extent (Hedges’ g = −0.71) as compared to event-based PM (Hedges’ g = −0.55). The impairment in PM is more likely due to failure in self-initiated retrieval of intention to be executed, rather than forgetting the content of the intention itself. Furthermore, factors such as intervening task complexity and the mediating role of other executive functions have also been proposed to be responsible for impaired PM in PD. (JINS, 2013, 19, 1–10)


2021 ◽  
Vol 22 (23) ◽  
pp. 12932
Author(s):  
Magdalena Kurnik-Łucka ◽  
Paweł Pasieka ◽  
Patrycja Łączak ◽  
Marcin Wojnarski ◽  
Michał Jurczyk

Background: an increased prevalence of gastro-duodenal ulceration was described almost sixty years ago as prodromal to idiopathic Parkinson’s disease, while duodenal ulcers have been rarely diagnosed in patients with schizophrenia. The cytoprotective role of dopamine in animal models of gastrointestinal ulcerations has also been described. Interestingly, Parkinson’s disease (PD) might share common pathophysiological links with inflammatory bowel disease (IBD) as epidemiological and genetic links already suggest. Thus, the aim of our study was to review the existing literature on the role of the gastrointestinal dopaminergic system in IBD pathogenesis and progression. Methods: a systematic search was conducted according to the PRISMA methodology. Results: twenty-four studies satisfied the predetermined criteria and were included in our qualitative analysis. Due to different observations (cross-sectional studies) as well as experimental setups and applied methodologies (in vivo and in vitro studies) a meta-analysis could not be performed. No ongoing clinical trials with dopaminergic compounds in IBD patients were found. Conclusions: the impairment of the dopaminergic system seems to be a significant, yet underestimated, feature of IBD, and more in-depth observational studies are needed to further support the existing preclinical data.


2013 ◽  
Vol 3 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Kapil Gudala ◽  
Dipika Bansal ◽  
Harini Muthyala

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