| Objective: To research the incidence rate of leucine-rich repeat kinase2(LRRK2)gene mutation in Chinese sporadic Parkinson’s disease (PD) patients, and thedifferences between gene mutation carriers and non-carriers in gender, age of onset,clinical symptoms, and drug therapeutic effects, Chinese PD patients who carriedLRRK2G2385R or R1628P variant or none of the variants were investigated in thepresent study.Methods: A total of135PD patients that were recruited from the First AffiliatedHospital of Dalian Medical University were enrolled in this study. PD diagnosis wasbased on the United Kingdom PD Society Brain Bank Criteria (1992). Patients with afamily of PD were not included. All patients have not family history of PD. Patients ortheir legal guardians signed Informed Consent for Diagnostic Genetic Test, andPD-related genes were detected in all patients. Eighty-six patients that have clinicaldetails and clinical follow-up observation for more than two years were selected fromthe above-mentioned135PD patients. The86patients were divided into two groups bygenetic test results. Patients carrying the risk allele of LRRK2G2385R or LRRK2R1628P variants were classified as LRRK2-PD, and the remaining patients withoutLRRK2variants were defined as idiopathic PD (IPD). Anticoagulant blood (usingsodium citrate)8~10ml and non-anticoagulant blood4~5ml were got from cubital vein.The names and ages of the patients, and the time points of drawing blood were labeled.DNA was isolated by phenol-chloroform DNA extraction method and stored at-20℃. LRRK2gene mutations were detected by PCR and DNA sequencing. The clinical dataof the86patients including gender, age of onset, duration of disease, motor symptoms(static tremor, myotoni, bradykinesia, postural instability and gait disorders, etc.),non-motor symptoms (constipation, disturbance sleep behavior, anxiety, depression,cognition dysfunction, etc.), motor complications (dyskinesia, wearing-off, dystonia,morning stiffness, motor fluctuation, etc.), and drugs used to treat Parkinson’s disease inthe two years follow-up observation were collected. Depressive symptoms wereevaluated by Center for Epidemiologic Studies Depression (CES-D) Scale. A cutoffscore of16is indicative of depression. Cognitive dysfunction was tested by the MinieMental State Examination (MMSE). A cutoff of24points indicated cognitiveimpairment. Disease severity before and after follow-up was assessed by UnifiedParkinson’s Disease Rating Scale (UPDRS)3.0, including total scores and scores of partⅠ, partⅡ, part Ⅲ, and part Ⅳ. Part Ⅱ, part Ⅲ of UPDRS scores were assessed in theON stage of the on-off phenomenon. The positive rate of LRRK2gene mutation wascalculated, and LRRK2-PD and IPD patients was compared in the age of onset, durationof disease, motor symptoms, non-motor symptoms, motor complications, efficacy oflevodopa, and UPDRS scores before and after follow-up observation. All the data wereanalyzed with SPSS13.0software.Results: The positive rate of LRRK2G2485R gene mutation was8.89%(12cases)and the positive rate of LRRK2R1628P gene mutation was1.48%(2cases).There are no significant differences between LRRK2-PD and IPD patients in thegender, age of onset, duration of disease, Hoehn-Yahr stage before follow-up, andUPDRS scores. For motor symptoms, there are no significant differences betweenLRRK2-PD and IPD patients in static tremor (78.6%in LRRK2-PD,87.5%in IPD),,myotonia (92.9%in LRRK2-PD,88.9%in IPD), bradykinesia (100.0%in LRRK2-PD,93.1%in IPD), and postural instability and gait disorders (78.6%in LRRK2-PD,80.6%in IPD). For non-motor symptoms, there are no significant differences betweenLRRK2-PD and IPD patients in constipation (57.1%in LRRK2-PD,77.8%in IPD),disturbance sleep behavior (71.4%in LRRK2-PD,88.9%in IPD), anxiety (35.7%in LRRK2-PD,38.9%in IPD), depression (42.9%in LRRK2-PD,50.0%in IPD), andcognitive dysfunction (0.0%in LRRK2-PD,8.3%in IPD). There are no significantdifferences between LRRK2-PD and IPD patients in CES-D Scale score (17.29±11.12in LRRK2-PD,16.19±9.67in IPD) and MMSE score (26.86±2.18in LRRK2-PD,27.24±2.69in IPD). For motor complications, there are no significant differencesbetween LRRK2-PD and IPD patients in dyskinesia (14.3%in LRRK2-PD,6.9%inIPD), wearing-off (14.3%in LRRK2-PD,5.6%in IPD), dystonia (14.3%in LRRK2-PD,9.7%in IPD), morning stiffness (7.1%in LRRK2-PD,15.3%in IPD), and motorfluctuation (14.3%in LRRK2-PD,6.9%in IPD). The effective rates of levodopa inLRRK2-PD and IPD patients are91.7%and87.5%, respectively, and there are nosignificant differences between the two groups. In LRRK2-PD patients, the totalUPDRS score and scores of part Ⅰ, partⅡ, part Ⅲ, and part Ⅳdid not changesignificantly after two year follow-up observation,before follow-up observation, totalUPDRS score:31.36±16.78, part Ⅰ score:2.21±1.76, part Ⅱ score:8.57±6.16, part Ⅲscore:19.07±9.68, part Ⅳ score:1.21±1.37; after follow-up observation, total UPDRSscore:29.50±15.83, part Ⅰ score:1.79±1.12, part Ⅱ score:8.57±6.16, part Ⅲ score:20.64±10.82, part Ⅳ score:0.50±0.94. In IPD patients, the total UPDRS score and partⅠ score did not change significantly compared with two years ago, before follow-upobservation, total UPDRS score:36.06±17.77, part Ⅰ score:2.49±1.96; after follow-upobservation, total UPDRS score:35.75±11.20, part Ⅰ score:2.19±1.15. The part Ⅱ,and part Ⅳ scores are reduced and the part Ⅲ score increased significantly comparedwith two years ago (before follow-up observation, part Ⅱ score:10.71±5.71, part Ⅲscore:21.64±11.56, part Ⅳ score:1.36±1.83; after follow-up observation, part Ⅱ score:8.43±4.07, part Ⅲ score:24.39±7.93, part Ⅳ score:0.92±1.34, P＜0.05).Conclusion:1. The positive rates of LRRK2G2485R and LRRK2R1628P gene mutation insporadic PD patients were8.89%and1.48%, respectively.2. The clinical features of LRRK2gene mutation carriers and non-carriers insporadic PD patients have no significant difference. 3. The drug efficacy on LRRK2gene mutation carriers and non-carriers in sporadicPD patients are different. |
PDF Full Text Request