scholarly journals Microarray Genotyping Identifies New Loci Associated with Dementia in Parkinson’s Disease

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1975
Author(s):  
Sungyang Jo ◽  
Kye Won Park ◽  
Yun Su Hwang ◽  
Seung Hyun Lee ◽  
Ho-Sung Ryu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Nucleotide Polymorphism ◽  
Primary Analysis ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Genomic Study

Dementia is one of the most disabling nonmotor symptoms of Parkinson’s disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56–0.78, p = 7.75 × 10−7). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68–3.79, p = 8.75 × 10−6) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD.

scholarly journals A specific amino acid motif of HLA-DRB1 mediates risk and interacts with smoking history in Parkinson’s disease

2019 ◽  
Vol 116 (15) ◽  
pp. 7419-7424 ◽  
Author(s):  
Jill A. Hollenbach ◽  
Paul J. Norman ◽  
Lisa E. Creary ◽  
Vincent Damotte ◽  
Gonzalo Montero-Martin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acids ◽  
Parkinson's Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Molecular Model ◽  
Peptide Binding ◽  
Smoking History ◽  
Disease Predisposition ◽  
History Of

Parkinson’s disease (PD) is a neurodegenerative disease in which genetic risk has been mapped to HLA, but precise allelic associations have been difficult to infer due to limitations in genotyping methodology. Mapping PD risk at highest possible resolution, we performed sequencing of 11 HLA genes in 1,597 PD cases and 1,606 controls. We found that susceptibility to PD can be explained by a specific combination of amino acids at positions 70–74 on the HLA-DRB1 molecule. Previously identified as the primary risk factor in rheumatoid arthritis and referred to as the “shared epitope” (SE), the residues Q/R-K/R-R-A-A at positions 70–74 in combination with valine at position 11 (11-V) is highly protective in PD, while risk is attributable to the identical epitope in the absence of 11-V. Notably, these effects are modified by history of cigarette smoking, with a strong protective effect mediated by a positive history of smoking in combination with the SE and 11-V (P = 10−4; odds ratio, 0.51; 95% confidence interval, 0.36–0.72) and risk attributable to never smoking in combination with the SE without 11-V (P = 0.01; odds ratio, 1.51; 95% confidence interval, 1.08–2.12). The association of specific combinations of amino acids that participate in critical peptide-binding pockets of the HLA class II molecule implicates antigen presentation in PD pathogenesis and provides further support for genetic control of neuroinflammation in disease. The interaction of HLA-DRB1 with smoking history in disease predisposition, along with predicted patterns of peptide binding to HLA, provide a molecular model that explains the unique epidemiology of smoking in PD.

Analysis of single nucleotide polymorphism rs415430 in the WNT3 gene in Parkinson’s disease in Russian population

2011 ◽  
Vol 26 (2) ◽  
pp. 47-49
Author(s):  
E. V. Filatova ◽  
M. I. Shadrina ◽  
E. Yu. Fedotova ◽  
P. A. Slominsky ◽  
S. N. Illarioshkin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Nucleotide Polymorphism ◽  
Russian Population ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Association ofCx43rs2071166 polymorphism with an increased risk for atrial septal defect

2017 ◽  
Vol 28 (3) ◽  
pp. 397-402 ◽  
Author(s):  
Ruoyi Gu ◽  
Wei Sheng ◽  
Xiaojing Ma ◽  
Guoying Huang
Keyword(s):  
Confidence Interval ◽  
Atrial Septal Defect ◽  
Odds Ratio ◽  
Septal Defect ◽  
Healthy Controls ◽  
Nucleotide Polymorphism ◽  
Chain Reaction ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Polymerase Chain

AbstractAtrial septal defect is one of the most common CHD. The pathogenesis of atrial septal defect still remains unknown.Cx43is the most prevalent connexin in the mammalian heart during development. Its genetic variants can cause several CHD. The aim of our study was to investigate the association of genetic variations of theCx43with sporadic atrial septal defect. A total of 450 paediatric patients were recruited, including 150 cases with atrial septal defect and 300 healthy controls. The promoter region ofCx43was analysed by sequencing after polymerase chain reaction. All data were analysed by using the Statistic Package for Social Science 19.0 software. The frequency of the single nucleotide polymorphism rs2071166 was significantly higher in atrial septal defect cases than in healthy controls. The CC genotype at rs2071166 site inCx43was correlated with an increased risk for atrial septal defect (p<0.0001, odds ratio=3.891, 95% confidence interval 1.948–7.772) and the C allele was positively correlated with atrial septal defect (p=0.007, odds ratio=1.567, 95% confidence interval 1.129–2.175). In conclusion, our results confirmed that rs2071166 inCx43may be relevant with an increased atrial septal defect risk.

rs73185306 C/T Is Not a Predisposing Risk Factor for Inherited Chromosomally Integrated Human Herpesvirus 6A/B

2019 ◽  
Author(s):  
Annabelle Mouammine ◽  
Annie Gravel ◽  
Isabelle Dubuc ◽  
Yassamin Feroz Zada ◽  
Sylvie Provost ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Risk Factor ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Human Herpesvirus ◽  
Chromosomal Integration ◽  
Nucleotide Polymorphism ◽  
Predisposing Factor ◽  
Single Nucleotide ◽  
Independent Cohort

Abstract Approximately 1% of people worldwide carry a copy of the human herpesvirus 6A or 6B (HHV-6A/B) in every cell of their body. This condition is referred to as inherited chromosomally integrated HHV-6A/B (iciHHV-6A/B). The mechanisms leading to iciHHV-6A/B chromosomal integration are yet to be identified. A recent report suggested that the rs73185306 C/T single-nucleotide polymorphism (SNP) represents a favorable predisposing factor leading to HHV-6A/B integration. After genotype analysis of an independent cohort (N = 11 967), we report no association between the rs73185306 C/T SNP and HHV-6A/B chromosomal integration (odds ratio, 0.90 [95% confidence interval, .54–1.51]; P = .69).

Deciphering variability in the role of interleukin-1β in Parkinson’s disease

2016 ◽  
Vol 27 (6) ◽  
pp. 635-650 ◽  
Author(s):  
Amene Saghazadeh ◽  
Carina C. Ferrari ◽  
Nima Rezaei
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 1Β ◽  
Heme Oxygenase 1 ◽  
Genetic Studies ◽  
Mitogen Activated Protein ◽  
Light Chain Enhancer

AbstractAlthough the role of inflammation in neurodegeneration has been well acknowledged, less is known on the issue of each cytokine in specific neurodegenerative diseases. In this review, we will present evidence elucidating that interleukin-1β (IL-1β) has a multi-faceted character in pathogenesis of Parkinson’s disease, which is a progressive neurodegenerative disorder. Increased levels of IL-1β were found in PD patients. Besides, PD symptoms were observed in IL-1β wild-type, but not deficient, animals. These lines of evidence suggest that IL-1β may contribute to the initiation or progression of PD. On the other hand, some studies reported decreased levels of IL-1β in PD patients. Also, genetic studies provided evidence suggesting that IL-1β may protect individuals against PD. Presumably, the broad range of IL-1β role is due to its interaction with both upstream and downstream mediators. Differences in IL-1β levels could be because of glia population (i.e. microglia and astrocytes), mitogen-activated protein kinase and nuclear factor κ light-chain-enhancer of activated B cells signaling pathways, and several mediators (including cyclooxygenase, neurotrophic factors, reactive oxygen species, caspases, heme oxygenase-1, and matrix metalloproteinases). Although far from practice at this point, unraveling theoretical therapeutic targets based on the up-down IL-1β neuroweb could facilitate the development of strategies that are likely to be used for pharmaceutical designs of anti-neurodegenerative drugs of the future.

scholarly journals The Single Nucleotide Polymorphism rs1014290 of the SLC2A9 Gene Is Associated with Uric Acid Metabolism in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-6
Author(s):  
Jiangfang Miao ◽  
Jing Liu ◽  
Li Xiao ◽  
Jiedi Zheng ◽  
Chunfeng Liu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Nucleotide Polymorphism ◽  
Uric Acid ◽  
Chinese Population ◽  
Acid Metabolism ◽  
Minor Allele ◽  
Control Group ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

Individuals with Parkinson’s disease (PD) have lower uric acid levels than those without PD, and the CC genotype and C minor allele of a single nucleotide polymorphism (SNP), rs1014290 of SLC2A9, are associated with lower uric acid levels. We investigated the association of rs1014290 with uric acid metabolism in a cohort of PD cases (220) and controls (110) in a Han Chinese population. Uric acid levels were determined and rs1014290 was assayed using a mutation-sensitive on/off switch technology. PD uric acid levels (291.65 ± 76.29 μmol/L) were significantly lower than the controls (325.73 ± 74.23 μmol/L, P<0.001, t-test). Individuals with rs1014290 TT and CT genotypes had higher uric acid levels, and those with the CC genotype had the lowest uric acid levels among both control and PD cases. The CC genotype and the C minor allele were statistically more frequent in the PD group compared to the control group. Those with the CC genotype had a statistically significant higher risk of PD than those with the TT or TC genotype (odds ratio [OR] = 2.249, 95% confidence interval [CI]: 1.129–4.480, and P=0.021). Thus, SLC2A9 rs1014290 is related to lower uric acid levels in PD patients and can be a risk factor for PD in the Han population.

Effect of modifiable risk factors in Parkinson’s disease: A case-control study looking at common dietary factors, toxicants, and anti-inflammatory medications

2021 ◽  
pp. 174239532110397
Author(s):  
Suzanna Shermon ◽  
Matthew Goldfinger ◽  
Alexander Morris ◽  
Brian Harper ◽  
Adena Leder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Case Control Study ◽  
Case Control ◽  
Dietary Factors ◽  
Anti Inflammatory ◽  
Red Meats ◽  
Control Study

Objective To investigate how common modifiable exposures, including dietary factors, select toxicants, and anti-inflammatory medications, may affect Parkinson’s disease. Methods Using surveys, a case-control study was conducted at a medical center, comparing Parkinson’s disease patients ( N  =  149) and healthy controls ( N  =  105). Subjects reported exposure to red meats, vegetables, alcohol, tobacco, anti-inflammatory medications, and pesticides. The relationship between exposures and Parkinson’s disease diagnosis was analyzed by logistic regression to generate odds ratio and 95% confidence interval. Results Consuming red meat “sometimes” or “always” was positively associated with Parkinson’s disease as compared to eating red meats “rarely” or “never”; (odds ratio  =   2.15, 95% confidence interval   =   1.06, 4.39; p  =  0.03) and (odds ratio   =   4.47, 95% confidence interval   =   1.67, 11.94; p  =  0.003), respectively. Exposure to pesticides showed a positive association with Parkinson’s disease (odds ratio  =   2.84, 95% confidence interval   =   1.34, 6.00; p  =  0.007). “Always” use of aspirin was inversely associated with Parkinson’s disease (odds ratio  =   0.32, 95% confidence interval   =   0.14, 0.70; p  =  0.004). “Ever” having used anti-histamines was inversely associated with Parkinson’s disease (odds ratio  =   0.37, 95% confidence interval  =  0.17, 0.81; p  =  0.01). Discussion Our study suggests that there are modifiable external factors that are associated with Parkinson’s disease. The present study can thus assist clinicians, policy makers, and people living with Parkinson’s disease in improving the experience and management of Parkinson’s disease.

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