Juan-Juan Du

Mutation Analysis of HTRA2 Gene in Chinese Familial Essential Tremor and Familial Parkinson’s Disease

Background. HTRA2 has already been nominated as PARK13 which may cause Parkinsons disease, though there are still discrepancies among these results. Recently, Gulsuner et al.s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinsons disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinsons disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinsons disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinsons disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinsons disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinsons disease and essential tremor in China.

Substantia Nigra Echogenicity Associated with Clinical Subtypes of Parkinson's Disease.

BACKGROUND It is debatable whether transcranial sonography (TCS) could be a biomarker for monitoring disease progression. Various phenotypes of Parkinsons disease (PD) may be a major reason contributing to the inconsistency. OBJECTIVE We classified PD patients into different subtypes and evaluated the correlation between SN echogenicity and disease progression. METHODS A total of 411 PD patients were included in this study. TCS evaluations of the substantia nigra (SN) were performed, and motor and non-motor symptoms were assessed by a series of rating scales in all PD patients. RESULTS Three hundred and thirteen patients had appropriate temporal acoustic bone windows, and they were divided into three subgroups according to disease onset age. SN hyperechogenicity (SN+) was found to be associated with age, gender, disease duration, H-Y stage and UPDRS-II scores in 220 middle-age onset patients. Regression analysis identified both disease duration and gender as independent predictors for SN+. When this distinct group was separated into male and female subgroups, the correlation between larger SN echogenicity (SNL) and disease duration was positive in males rather than females. When these middle-age onset male patients were classified as tremor dominant (TD) and non-TD subtypes, it turned out that correlation between disease duration and SNL only existed in male non-TD PD patients. CONCLUSIONS Our study demonstrated correlation between the size of SN echogenicity and disease duration in Chinese patients with PD who were male non-TD subtypes with middle-age onset, suggesting the formation of SN echogenicity might be a dynamic process following disease progression in this distinct subtype.

Validation of the Parkinson Fatigue Scale in Chinese Parkinson's disease patients

Fatigue is a common nonmotor symptom in Parkinsons disease (PD); however, the Parkinsons disease fatigue scale (PFS), which is designed to measure fatigue in PD, has not been validated in China. The aim of this study was to determine the validity and reliability of the Chinese version of the PFS in PD patients.

Clinical correlates of decreased plasma coenzyme Q10 levels in patients with multiple system atrophy

INTRODUCTION Multiple system atrophy (MSA) is a progressive neurodegenerative disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the cerebellum and blood samples of MSA patients. But few studies focused on the associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed to quantify plasma COQ10 and characterize its association with clinical features. METHODS We recruited 40 patients with MSA, 30 patients with Parkinsons disease (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The basic demographic data, motor symptoms, and non-motor symptoms were also assessed. RESULTS Plasma COQ10 levels were significantly different in MSA, PD, and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA patients were lower than that in controls after adjusting for age, gender, and total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity of 97.5% was calculated with the receiver operating characteristic curve. However, COQ 10 levels did not discriminate between the MSA and PD groups (P = 0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms only in MSA-C patients (b = -0.025, P = 0.009). CONCLUSION The association between decreased COQ10 levels and the severity of motor symptoms in MSA-C patients promotes further research. Plasma COQ10 levels alone may not be a reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in the differential diagnosis of MSA vs PD.

Lack of Association Between DNMT3B Polymorphisms and Sporadic Parkinson’s Disease in a Han Chinese Population

Recently, several single nucleotide polymorphisms (SNPs; rs34094401 on RAD51B, rs41309351 on CPXM1, rs143555311 on MPHOSPH10, rs141620200 on SERPINA1, and rs2424913 on DNMT3B) have been associated with Parkinson’s disease (PD) in Caucasians [1–3]. Considering the genetic variance among different ethnic populations, it is essential to know whether these candidate SNPs are also associated with PD in other ethnic cohorts. Therefore, we investigated these newly-reported risk SNPs in 249 PD patients and 239 controls to test their association with PD. There was no difference in age (P = 0.425) and gender (P = 0.718) between the PD and control groups (Table S1). Alleles and genotypes of the candidate SNPs are shown in Table S2. Hardy–Weinberg equilibrium was calculated for each SNP, and no significant deviation was found. The minor allele frequencies of rs34094401 (RAD51B), rs41309351 (CPXM1), rs143555311 (MPHOSPH10), and rs141620200 (SERPINA1) were all zero in both the PD and control groups. Two adjacent SNPs, rs9941620 MPHOSPH10 and rs75826787 DNMT3B, were not associated with PD risk in either of the models. As rs75826787 and rs2424913 are on the same chromosome, linkage disequilibrium was analyzed, and none was found between them (Table S3). Notably, for rs2424913 on DNMT3B, the frequency of the minor allele ‘‘C’’ in the control group (0.84%) was more than twice the minor allele frequency in the PD group (0.40%), and the odds ratio (OR) was 0.48. However, this difference was not statistically significant, either in allelic association (P = 0.443), the dominant model (P = 0.443), or the additive model (P = 0.394) (Table S2). Interestingly, the ‘‘C’’ allele of rs2424913 showed an even lower odds ratio in females (OR 0.31) under subgroup analysis based on gender (Table 1), though this association was not statistically significant (P = 0.356). Two studies [3, 4] have investigated the association between rs2424913 and PD risk in a Brazilian population of European ancestry and a South Chinese Han population. The latter was included in our meta-analysis. In total, 736 PD patients and 724 controls were included. The fixed effect model was applied since there was no heterogeneity (I = 0%). The results showed that rs2424913 was not significantly associated with PD in the Han Chinese population (P = 0.42 for allelic association, and P = 0.64 for the dominant model). In addition, the result of subgroup analysis based on gender in meta-analysis was similar to the results in our cohort (Table S4, Fig. S1). To our knowledge, this is the first study on the association of rs75826787 (DNMT3B), rs34094401 Hong Pan and Jun-Yi Shen have contributed equally to this work.

Prevalence and risk factors for depression and anxiety in Chinese patients with Parkinson disease

BackgroundAnxiety and depression are common in Parkinson disease and both are important determinants of quality of life in patients. Several risk factors are identified but few research have investigated general and Parkinson’s disease (PD)-specific factors comprehensively. The aim of this work was to explore PD-specific and -non-specific risk factors for PD with depression or anxiety.MethodsA cross-sectional survey was performed in 403 patients with PD. Multivariate logistic analysis was used to investigate the prevalence and risk factors for the depression and anxiety in PD. The data of patients included demographic information, medicine history, disease duration, age at onset (AAO), family history, anti-parkinsonism drug, modified Hoehn and Yahr staging (H-Y) stage, scales of motor and non-motor symptoms and substantia nigra (SN) echogenic areas.Results403 PD patients were recruited in the study. Depression and anxiety were present in 11.17% and 25.81% respectively. Marital status, tumor, higher Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) II score, dyskinesia, higher Hamilton Anxiety Rating Scale (HARS) score and lower the Parkinson’s disease sleep scale (PDSS) score were associated with depression in PD. female gender, higher rapid eye movement behavior disorder Questionnaire-Hong Kong (RBD-HK) score, higher Hamilton Deprssion Rating Scale (HAMD) score, higher the scale for outcomes in PD for autonomic symptoms (SCOPA-AUT)score and larger SN echogenic areas were associated with anxiety. Neither depression nor anxiety was related to any anti-parkinsonism drugs.ConclusionsThe prevalence of depression and anxiety in the current PD patients was 11.17% and 25.81% respectively. Disease of tumor, currently having no partner, severer motor function, dyskinesia, poorer sleep quality and anxiety were risk factors for PD with depression. Female, depression, rapid eye movement behavior disorder (RBD), autonomic dysfunction and larger SN area were risk factors for PD with anxiety.