Parkinson's Disease
Conditions
Keywords
Parkinson's disease, synaptic correlation function, key gene
Brief summary
The research team used meta-analytical statistical methods to integrate the results of different research groups on Parkinson's disease, using meta-analysis to find key genes related to the pathogenesis and development of Parkinson's disease, and to make small clinical results. The verification of the sample, the internal mechanism of the pathogenesis of Parkinson's disease and provide guidance and reference for subsequent experimental research.
Detailed description
Parkinson's disease (PD) is a relatively common degenerative disease of the central nervous system. As society gradually becomes aging, the number of PD patients is increasing, but its exact pathogenesis is still not fully understood. May be related to genetic factors, environmental factors, immunological abnormalities, mitochondrial dysfunction and oxidative stress, ageing, apoptosis and other factors; the current genetic diagnosis is in the ascendant, making the understanding of the etiology and pathogenesis of Parkinson's disease more In-depth, provide more basis and means for the pathogenesis and development of Parkinson's disease, but due to the number of individual samples, operational norms and platform differences, different research groups have great differences in the results of gene chip research on Parkinson's mechanism, resulting in the reliability is poor; In order to improve the credibility of the pathogenesis of Parkinson's disease and the development of genetic diagnosis, the investigators use the statistical means of meta-analysis to integrate the results of the chip research on Parkinson's disease in different research groups and find synaptic correlation function may be closely related to the development of Parkinson's disease, PPP2CA, PPP3CB, SYNJ1, NSF, CYCS genes may be key genes in the pathogenesis of Parkinson's disease, and the expression of these genes is related to the pathogenesis and development of PD patients. the investigators will conduct a small sample validation in the clinic to explore the intrinsic mechanism of Parkinson's disease and follow-up experimental research provides guidance and reference.
Interventions
DIAGNOSTIC_TESTgenetic diagnosis
The venous blood of the two groups of patients was taken for genetic testing, and the expression levels of PPP2CA, PPP3CB, SYNJ1, NSF and CYCS were extracted by pre-processing the genetic data of PD and non-PD patients.
Sponsors
Zhujiang Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* PD group： * Patients who meet the 2016 China Parkinson's diagnostic criteria and the 2015 International Parkinson's and Movement Disorders Association (MDS) Parkinson's disease diagnostic criteria * Newly diagnosed primary PD patients, diagnosed within 3-6 months * Informed consent to the study * Age \> 18 older * Non-PD group: * Age, gender-matched PD group * Non-PD, non-PDS, non-neurological degenerative disease, patients without inflammatory disease and related family history * Informed consent to the study * Age \> 18 older
Exclusion criteria
* Severe craniocerebral trauma patients * Disturbance of consciousness * Severe organic diseases, cerebral hemorrhage, cerebral thrombosis, severe coronary heart disease and lung disease, severe liver and kidney dysfunction, severe diabetes, severe hearing And visual impairment * History of severe brain tumors, encephalitis or brain surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Parkinson's Key Gene | 3 days | The blood of patients were taken for genetic testing and relative expression levels of the genes(These genes expression relative to a house keeping gene:GAPDH) for PPP2CA, PPP3CB, SYNJ1, NSF were extracted.The method we used is RT-PCR. |
| Unified Parkinson's Disease Rating Scale 3.0（UPDRS 3.0） | 2 days | The total score ranges from 0 to 199( minimum score is 0 and maximum scores is 199), in which a lower score denotes a better perception of the patient's. Scoring the mental, behavioral and emotional, daily living activities, exercise tests, and drug treatment complications associated with UPDRS3.0 in patients with Parkinson's disease;each item 0-4 points, total score 199 points, 0-50 points: limb and body mild dysfunction, posture response normal;51-100 points: mild postural reaction disorder, self-care in daily life, loss of labor force;101-199: obvious postural reaction disorder, loss of daily life and labor force, may need help to get up and confined to wheelchair life;The more severe the symptoms of Parkinson's disease, the higher the score. |
| Non-motor Symptom Scale (NMSS) | 2 days | Scoring based on the patient's own situation in the last month Severity: 1 = mild; 2 = moderate; 3 = severe Frequency: 1 = very little (less than once a week); 2 = often (1 time a week); 3 = frequent (a few times a week); 4 = very frequent (every day or persist) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Parkinson's Disease Group 1. Patients who meet the 2016 China Parkinson's diagnostic criteria and the 2015 International Parkinson's and Movement Disorders Association (MDS) Parkinson's disease diagnostic criteria;
2. Newly diagnosed primary PD patients, diagnosed within 3-6 months;
3. informed consent to the study;
4. age \> 18 older.
genetic diagnosis: The venous blood of the three groups of patients was taken for genetic testing, and the expression levels of PPP2CA, PPP3CB, SYNJ1, NSF and CYCS were extracted by pre-processing the genetic data of PD ,PPS patients and healthy controls. | 90 |
| Healthy Controls healthy group inclusion criteria: age, gender-matched PD group, non-PD, non-PDS, non-neurological degenerative disease, patients without inflammatory disease and related family history; informed consent to the study; age \> 18 older.
genetic diagnosis: The venous blood of the three groups of patients was taken for genetic testing, and the expression levels of PPP2CA, PPP3CB, SYNJ1, NSF and CYCS were extracted by pre-processing the genetic data of PD and PPS patients and healthy controls . | 125 |
| Parkinson-plus Syndrome Group 1\. patients with Parkinson-plus syndrome were diagnosed according to 2017 MDS progressive supranuclear paralysis and 2017 clinical diagnostic criteria for MDS progressive supra palsy (PSP patients) and Giman standard, the 2008 American board of neurology (AAN) MSA diagnostic consensus.2.informed consent to the study; 3.age \> 18 older.
genetic diagnosis: The venous blood of the three groups of patients was taken for genetic testing, and the expression levels of PPP2CA, PPP3CB, SYNJ1, NSF and CYCS were extracted by pre-processing the genetic data of PD and PPS patients and healthy controls . | 23 |
| Total | 238 |
Baseline characteristics
| Characteristic | Total | Parkinson's Disease Group | Healthy Controls | Parkinson-plus Syndrome Group |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 105 Participants | 44 Participants | 54 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 133 Participants | 46 Participants | 71 Participants | 16 Participants |
| Age, Continuous | 63.40 years STANDARD_DEVIATION 11.09 | 63.66 years STANDARD_DEVIATION 11.94 | 63.42 years STANDARD_DEVIATION 10.99 | 62.30 years STANDARD_DEVIATION 8.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 238 Participants | 90 Participants | 125 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 238 Participants | 90 Participants | 125 Participants | 23 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 238 Participants | 90 Participants | 125 Participants | 23 Participants |
| Sex: Female, Male Female | 108 Participants | 34 Participants | 59 Participants | 15 Participants |
| Sex: Female, Male Male | 130 Participants | 56 Participants | 66 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 0 / 125 | 0 / 23 |
| other Total, other adverse events | 0 / 90 | 0 / 125 | 0 / 23 |
| serious Total, serious adverse events | 0 / 90 | 0 / 125 | 0 / 23 |
Outcome results
Primary
Non-motor Symptom Scale (NMSS)
Scoring based on the patient's own situation in the last month Severity: 1 = mild; 2 = moderate; 3 = severe Frequency: 1 = very little (less than once a week); 2 = often (1 time a week); 3 = frequent (a few times a week); 4 = very frequent (every day or persist)
Time frame: 2 days
Population: Data were not collected.
Primary
Parkinson's Key Gene
The blood of patients were taken for genetic testing and relative expression levels of the genes(These genes expression relative to a house keeping gene:GAPDH) for PPP2CA, PPP3CB, SYNJ1, NSF were extracted.The method we used is RT-PCR.
Time frame: 3 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parkinson's Disease Group | Parkinson's Key Gene | SYNJ1 | 0.924 gene expression relative to GAPDH |
| Parkinson's Disease Group | Parkinson's Key Gene | PPP3CB | 1.669 gene expression relative to GAPDH |
| Parkinson's Disease Group | Parkinson's Key Gene | PPP2CA | 1.502 gene expression relative to GAPDH |
| Parkinson's Disease Group | Parkinson's Key Gene | NSF | 1.002 gene expression relative to GAPDH |
| Healthy Controls | Parkinson's Key Gene | SYNJ1 | 4.662 gene expression relative to GAPDH |
| Healthy Controls | Parkinson's Key Gene | PPP2CA | 3.653 gene expression relative to GAPDH |
| Healthy Controls | Parkinson's Key Gene | PPP3CB | 2.237 gene expression relative to GAPDH |
| Healthy Controls | Parkinson's Key Gene | NSF | 3.058 gene expression relative to GAPDH |
| Parkinson-plus Syndrome Group | Parkinson's Key Gene | PPP2CA | 0.916 gene expression relative to GAPDH |
| Parkinson-plus Syndrome Group | Parkinson's Key Gene | SYNJ1 | 5.206 gene expression relative to GAPDH |
| Parkinson-plus Syndrome Group | Parkinson's Key Gene | NSF | 1.408 gene expression relative to GAPDH |
| Parkinson-plus Syndrome Group | Parkinson's Key Gene | PPP3CB | 2.320 gene expression relative to GAPDH |
Comparison: we use the method of RT-PCR to detect the relative expression level of PPP2CA gene in Parkinson's disease group(90 participants), healthy controls group(125 participants) and Parkinson-plus syndrome group(23 participants).This gene expression is relative to a house keeping gene GAPDH.The data were processed using 2-△△Ct. ΔCT(test) = CT(target, test) - CT(ref, test), ΔCT(calibrator) = CT(target, calibrator) - CT(ref, calibrator),ΔΔCT = ΔCT(test) - ΔCT(calibrator).p-value: <0.001Kruskal-Wallis
Comparison: we use the method of RT-PCR to detect the relative expression level of SYNJ1 gene in Parkinson's disease group(90 participants), healthy controls group(125 participants) and Parkinson-plus syndrome group(23 participants).This gene expression is relative to a house keeping gene GAPDH.The data were processed using 2-△△Ct. ΔCT(test) = CT(target, test) - CT(ref, test), ΔCT(calibrator) = CT(target, calibrator) - CT(ref, calibrator),ΔΔCT = ΔCT(test) - ΔCT(calibrator).p-value: <0.001Kruskal-Wallis
Comparison: we use the method of RT-PCR to detect the relative expression level of PPP3CB gene in Parkinson's disease group(90 participants), healthy controls group(125 participants) and Parkinson-plus syndrome group(23 participants).This gene expression is relative to a house keeping gene GAPDH.The data were processed using 2-△△Ct. ΔCT(test) = CT(target, test) - CT(ref, test), ΔCT(calibrator) = CT(target, calibrator) - CT(ref, calibrator),ΔΔCT = ΔCT(test) - ΔCT(calibrator).p-value: 0.149Kruskal-Wallis
Comparison: we use the method of RT-PCR to detect the relative expression level of NSF gene in Parkinson's disease group(90 participants), healthy controls group(125 participants) and Parkinson-plus syndrome group(23 participants).This gene expression is relative to a house keeping gene GAPDH.The data were processed using 2-△△Ct. ΔCT(test) = CT(target, test) - CT(ref, test), ΔCT(calibrator) = CT(target, calibrator) - CT(ref, calibrator),ΔΔCT = ΔCT(test) - ΔCT(calibrator).p-value: <0.001Kruskal-Wallis
Primary
Unified Parkinson's Disease Rating Scale 3.0（UPDRS 3.0）
The total score ranges from 0 to 199( minimum score is 0 and maximum scores is 199), in which a lower score denotes a better perception of the patient's. Scoring the mental, behavioral and emotional, daily living activities, exercise tests, and drug treatment complications associated with UPDRS3.0 in patients with Parkinson's disease;each item 0-4 points, total score 199 points, 0-50 points: limb and body mild dysfunction, posture response normal;51-100 points: mild postural reaction disorder, self-care in daily life, loss of labor force;101-199: obvious postural reaction disorder, loss of daily life and labor force, may need help to get up and confined to wheelchair life;The more severe the symptoms of Parkinson's disease, the higher the score.
Time frame: 2 days
Population: The Unified Parkinson's Disease Rating Scale 3.0 is just suitable for PD patients,so there are no relative result for the group of healthy controls and Parkinson-plus syndrome group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parkinson's Disease Group | Unified Parkinson's Disease Rating Scale 3.0（UPDRS 3.0） | 61.352 score on a scale | Standard Deviation 29.611 |