Late-onset Parkinson's Disease Patients Research Articles

Comparison of Cognitive Profile in Young- and Late-onset Parkinson's Disease Patients.

Background:Cognitive impairment is increasingly being recognized as a major cause of morbidity and increased dependence over the caregivers in Parkinson's disease (PD) patients.Objective:The present study aimed to compare the cognition testing in young- and late-onset PD patient.Methods:Sixty PD patients (20 young onset and 40 late onset) fulfilling UKPDS Brain Bank diagnostic criteria were enrolled in the study. Patients were assessed clinically and using scales for cognition testing such as Scales for Outcomes in PDCognition (SCOPA-COG), Unified Parkinson's Disease Rating scale (motor part), and Hoehn and Yahr staging.Results:Young-onset group comprised 20 (33.3%) and late-onset group comprised 40 (66.7%) patients. Most of the young- and late-onset patients, 15 (75%) and 21 (52.5%), had SCOPA-COG score in the range of 30–39, respectively. On comparison between young- and late-onset groups, SCOPA-COG score's mean ± standard deviation (SD) for young and late onset was 32.60 ± 2.52 and 30.30 ± 3.65, respectively, with statistical significance (P = 0.01). SCOPA-COG score's mean ± SD for mild, moderate, and severely impaired PD patients was 31.48 ± 3.19, 30.60 ± 3.24, and 23.50 ± 3.53, respectively, which on group comparisons (ANOVA) were statistically significant (P = 0.004). However, the SCOPA-COG score was statistically insignificant with respect to disease duration.Conclusion:There was statistically significant difference in SCOPA-COG score between young- and late-onset PD patients and in patients with more severe motor impairment.

Patterns of striatal functional connectivity differ in early and late onset Parkinson's disease.

To map functional connectivity (FC) patterns of early onset Parkinson's disease (EOPD) and late onset PD (LOPD) in drug-naïve early stage. MRI was used to assess atrophy and resting-state FC focusing on striatal subregions of EOPD and LOPD in two subgroups of 18 patients matched for disease duration and severity, relative to age- and sex- matched healthy controls. Compared with controls, both PD subgroups showed FC alterations in cortico-striatal and cerebello-striatal loops but with different patterns in resting state. EOPD patients showed widespread increased FC between striatum and sensorimotor cortex, middle frontal gyrus, superior and inferior parietal lobules, superior and inferior temporal gyri, and cerebellum. While LOPD patients were evidenced with increased FC in cerebello-striatal circuit and decreased FC between orbitofrontal gyrus and striatum. In addition, Unified Parkinson's Disease Rating Scale part III scores were negatively correlated with the increased FC between the caudate nucleus and sensorimotor cortex (r=-0.571, p=0.013) in EOPD patients, while negatively correlated with the increased FC between the putamen and cerebellum (r=-0.478, p=0.045) in LOPD patients, suggesting that increased FC is here likely to reflect compensatory mechanism. FC changes in EOPD and LOPD share common features and have differences, which may suggest that the responses to defective basal ganglia are different between the two subtypes. Improved insights into the onset-related subtypes of PD and its disruptive FC pattern will be valuable for improving our understanding of the pathogenesis of the disease.

Clinical phenotype and risk of levodopa-induced dyskinesia in Parkinson's disease.

It is unclear whether patients with different clinical phenotypes of Parkinson's disease (PD) differ in their risk of developing levodopa-induced dyskinesia. We evaluated the possible association between clinical phenotypes and risk of levodopa-induced dyskinesia in PD patients using a case-control design. The FRAGAMP study is a large Italian multicenter study. Patients affected by PD diagnosed according to the Gelb's criteria were enrolled and underwent a face-to-face interview. Clinical scales were used to evaluate motor and cognitive impairment. Presence of dyskinesia was assessed by the item 32 of the UPDRS section IV. On the basis of the most prominent motor symptoms at onset PD, patients were classified as tremor-dominant, akinetic-rigid, or mixed type. 485 PD patients (292 men; mean age 65.6±9.8) were enrolled in the study of whom 128 (26.4%) presented levodopa-induced dyskinesia. Of the 485 patients, 311 (64.1%) were classified as tremor-dominant, 104 (21.4%) as Akinetic-Rigid and 70 (14.4%) as mixed type. Multivariate logistic regression analysis showed a significant negative association between tremor-dominant phenotype and levodopa-induced dyskinesia (adjusted OR 0.48; 95% CI 0.23-1.00; p value 0.05). When analysis was stratified by age at onset a stronger negative association was found among the late onset (>50years) PD patients (OR 0.28; 95% CI 0.11-0.70; p value 0.007) while no association was found among patients with an early onset. Our findings support the hypothesis that the occurrence of resting tremor as an initial manifestation of PD may predict a lower probability of developing levodopa-induced dyskinesia.

Cognitive profile of Parkinson's disease patients: a comparative study between early-onset and late-onset Parkinson's disease

Aim: To investigate the influence of onset age on the occurrence and progression of cognitive dysfunction using neuropsychological tests and the electrophysiological component P300 in both early-onset Parkinson's disease (EOPD) and late-onset Parkinson's disease (LOPD) patients. Methods: A cohort of 76 EOPD patients and 166 LOPD patients was recruited for this study. Demographic information and clinical features, including age, disease duration, education level, family history, the Unified Parkinson's Disease Rating Scale, the Hoehn and Yahr stage, and depression scores were documented for each patient. The Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA), Wechsler Adult Intelligence Scale – Revised, Chinese version (WAIS-RC) and Wechsler Memory Scale – Revised, Chinese version (WMS-RC) were used. In addition, P300 was also examined to assess cognitive function. Results: Although EOPD patients had longer disease duration, their cognitive dysfunction progressed more slowly. The MoCA tests revealed that EOPD patients had higher scores in visuospatial function, attention, delayed recall, and orientation than the LOPD patients. The difference between the two groups on the WMS-RC test did not reach significance, whereas the scores in executive function, visuospatial function and attention as measured on the WAIS-RC test were significantly lower in the LOPD group. In addition, P300 latencies were markedly delayed and P300 amplitudes were reduced in the LOPD group. Conclusions: The current findings demonstrated that cognitive dysfunction progressed more slowly in the EOPD group. Although the LOPD patients exhibited shorter disease durations, their cognitive abilities, including executive function, visuospatial function and attention, may have been impaired.

Diurnal drooling in Chinese patients with Parkinson's disease

ObjectiveThe aim of this study is to explore the prevalence and clinical correlates of diurnal drooling in Chinese patients with Parkinson's disease (PD). MethodsA cross-sectional analysis of 518 Chinese patients with PD was conducted. Each subject was categorized as a diurnal “drooler” or a “non-drooler” using the Non-Motor Symptoms Scale (NMSS). ResultsOne hundred and twenty-one (23.4%) patients exhibited diurnal drooling. Diurnal drooling was reported more frequently in male and late-onset PD patients (p<0.05). The levodopa equivalent daily doses, mean age and disease duration, the percentages of PD family history and levodopa or entacapone use, the incidences of dysarthria, dysphagia and fluctuation, and the Unified PD Rating Scale (UPDRS) part III, NMSS, Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and PD Questionnaire 39 (PDQ-39) scores in droolers were significantly greater than in non-droolers (p<0.05). The percentage of benzhexol use in non-droolers was significantly higher than in droolers (p<0.05). The Frontal assessment battery (FAB) and Montreal Cognitive Assessment (MoCA) scores were not different between the droolers and non-droolers. The forward binary logistic regression model indicated that dysarthria, male sex, age, UPDRS part III, sexual dysfunction and a family history of PD were associated with diurnal drooling. ConclusionsDiurnal drooling is a relatively common debilitating symptom in Chinese PD patients. It is not only related to male sex, age, dysarthria and PD family history, but also correlates with motor and non-motor severity especially sexual dysfunction of PD. However, it is not related to cognition.

Prevalence and clinical correlates of drooling in Parkinson disease: a study on 518 Chinese patients.

The prevalence and clinical correlates of drooling in Chinese patients with Parkinson disease (PD) are unknown. A cross-sectional analysis of 518 Chinese patients with PD was conducted. Assessments included Unified PD Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), PD Questionnaire-39 (PDQ-39), Frontal assessment battery (FAB) and Montreal Cognitive Assessment (MoCA). Two hundred and seventy-three PD patients (52.7%) reported drooling (droolers). Drooling occurred more frequently in the late-onset PD patients than the early-onset PD patients (p < 0.05). Droolers had higher levodopa equivalent daily doses, higher incidences of dysarthria, dysphagia and fluctuation, higher scores for the UPDRS part III, NMSS, HAMD and HAMA, and higher scores for the mobility, activities of daily life, stigma and communication subdomains of the PDQ-39 than the non-droolers (p < 0.05). The percentage of benzhexol use in the non-droolers was significantly higher than the droolers (p < 0.05). The FAB and MoCA scores between the droolers and non-droolers were not different. The binary logistic regression analysis indicated that dysarthria, dysphagia, benzhexol use, and a lower score for the naming domain of the MoCA were associated with drooling. Drooling is a relatively common disabling symptom in Chinese PD patients. Patients with dysarthria, dysphagia and naming disorder are likely to experience drooling. Drooling is not correlated with disease duration and motor severity of PD.

SNCA variants rs2736990 and rs356220 as risk factors for Parkinson’s disease but not for amyotrophic lateral sclerosis and multiple system atrophy in a Chinese population

Previous studies found that polymorphisms rs2736990 and rs356220 in the alpha-synuclein (SNCA) gene increase the risk for Parkinson's disease (PD) in a Caucasian population. In consideration of the overlapping of clinical manifestations and pathologic characteristics among PD, amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA), the possible associations of these 2 polymorphisms and 3 neurodegenerative diseases were studied in the Chinese population. A total of 1011 PD, 778 sporadic ALS (SALS), 264 MSA patients, and 721 healthy controls (HCs) were studied. All subjects were genotyped for the 2 polymorphisms using polymerase chain reaction and direct sequencing. Significant differences in the genotype frequencies (p = 0.0188 and 0.0064, respectively) and minor allele frequencies (MAFs) (p = 0.0065 and 0.0095, respectively) of rs2736990 and rs356220 were observed between the PD patients and HCs. Moreover, significant differences were found between the early-onset PD patients (<50 years) and matched controls but not in the late-onset PD patients (≥50 years). However, no differences were observed between subgroups with regard to clinical features, such as sex, onset symptoms (tremor or rigidity), cognition (normal or abnormal), and anxiety and depression (presence or absence). No significant differences were found in the genotype frequencies and MAFs of these 2 single-nucleotide polymorphisms between SALS patients and HCs and between MSA patients and HCs. No significant differences were found between subgroups with regard to the clinical presentation of SALS and MSA. Our results show that rs2736990 and rs356220 in SNCA decreased the risk for PD in a Chinese population. These candidate polymorphisms were unlikely to be the causes of SALS and MSA in this population.

HTRA2 variations in Taiwanese Parkinson’s disease

Mutations in HTRA2 have been reported to associate with Parkinson's disease (PD). This study investigates if the genetic variants in HTRA2 contribute to Taiwanese PD. HTRA2 cDNA fragments from 80 patients with early-onset PD (onset ≤50years) were sequenced. The identified variants were further examined for a cohort of PD and ethnically matched controls. A novel heterozygous R36W was identified in one early-onset and two late-onset PD patients, which was absent in 606 normal controls. The clinical features and 99mTc-TRODAT-1 SPECT image of the early-onset patient carrying R36W were similar to that of idiopathic PD. The R36W mutation of the patient was inherited from his mother whose SPECT revealed asymmetric reduction of 99mTc-TRODAT-1 uptake in the left striatum, suggesting that the defect of the nigrostriatal pathway may be attributable to the R36W in this family. Protein subcellular fractionation further revealed that R36W affected the processing of the proprotein after transport into mitochondria. Although the functional assays are promising, a larger cohort of both cases and controls should be screened to clarify the role of R36W in Taiwanese PD pathogenicity.

Gender and onset age-related features of non-motor symptoms of patients with Parkinson's disease – A study from Southwest China

BackgroundNon-motor symptom (NMS) differences between male Parkinson's disease (PD) and female PD, and between early-onset PD (EOPD) and late-onset PD (LOPD) in Chinese populations remain largely unknown. MethodsA total of 522 PD patients from Southwest China were included. Patients were assessed using the Non-Motor Symptom Scale (NMSS) and Unified PD Rating Scale (UPDRS). ResultsMore NMS and significantly higher NMSS score were found in LOPD patients than in EOPD patients (9.3 ± 5.9 vs. 7.7 ± 5.6, P = 0.005; 37.4 ± 32.2 vs. 30.5 ± 28.9, P = 0.018), while no such differences were found between male and female patients. The NMS of gastrointestinal and urinary domains were more common in LOPD patients than in EOPD patients, whereas sexual dysfunction was more common in EOPD than in LOPD. The sleep/fatigue domain, the mood/apathy domain and “pain” symptoms were more prevalent and severe in female patients than in male patients while urinary symptoms were more common and severe in male patients. Significant positive correlations were observed between disease duration, Hoehn & Yahr stage, UPDRS Ⅲ, and NMSS score in the total sample, subgroups of both male and female patients as well as both EOPD and LOPD patients. ConclusionsNMS are common in the Chinese PD population. LOPD patients are likely to present with more and severe NMS than EOPD patients. Males are subjected to urinary symptoms and females are subjected to mood/apathy, sleep and pain symptoms.

Age at onset influences neurodegenerative processes underlying PD with levodopa-induced dyskinesias

PurposeRecently, we demonstrated that PD patients with levodopa-induced dyskinesias are characterized by neuroanatomical and functional changes involving the prefrontal cortex. When compared with non-dyskinetic PD patients, dyskinetic PD patients showed increased volume of the inferior frontal cortex and a dysfunctional imbalance between this region and the supplementary motor area during motor task. In the current study, we investigated the impact of age at onset of the disease on the neuroanatomical characteristics of dyskinetic patients, because it is well known that early-onset PD patients usually develop dyskinesias sooner with respect to late-onset PD. MethodsWhole-brain voxel-wise investigations of gray matter volume and cortical thickness were carried out in dyskinetic (n = 33), non-dyskinetic PD patients (n = 33) and in age-sex-matched healthy controls (n = 40). Neuroimaging analyses were performed separately according to the age at onset (early < 50 y > late). ResultsIndependent of age at onset, dyskinetic PD patients showed altered morphology in the inferior frontal cortex when compared with non-dyskinetic patients. Moreover, additional significant abnormalities emerged in the early- and late-onset PD patients when compared to controls. In fact, early-onset dyskinetic patients showed increased volume in a large cluster of the midbrain encompassing substantia nigra and red nucleus, whereas late-onset dyskinetic patients were characterized by abnormal gray matter increase in the supplementary motor area. DiscussionOur findings demonstrate different patterns of brain abnormalities in patients with LID according to age at onset, highlighting the role of the nigral pathology in early-onset and of the cortical pathology in late-onset patients with PD.

Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease

The diagnosis of Parkinson's disease (PD) is currently based on the clinical evaluation of extrapyramidal signs with a considerable error rate. The identification of specific markers might allow PD diagnosis before the onset of classical motor symptoms. By two-dimensional electrophoresis we identified proteome alterations in T-lymphocytes of 17 control subjects and 15 PD patients. The observed changes were used to build predictive models that were verified by the leave-one-out cross-validation. We further built two functions able to stage the subjects. We chose to verify by Western blotting the identity of spots corresponding to β-fibrinogen and transaldolase, two recurrent proteins in six out of 20 spots. β-Fibrinogen levels are lowered in PD patients, whereas a heavy transaldolase set of isoforms was more abundant. Eventually, we identified a list of seven proteins showing different levels in early-onset with respect to late-onset PD patients.

Factors influencing the development of early- or late-onset Parkinson’s disease in a cohort of South African patients

Neurodegenerative disorders such as Parkinson's disease (PD) contribute significantly to global disease burden. PD can be categorised into early-onset PD (EOPD) with an age at onset (AAO) of ≤50 years and late-onset PD (LOPD) with an AAO of 50 years. To identify factors influencing EOPD and LOPD development in a group of patients in South Africa (SA). A total of 397 unrelated PD patients were recruited from the Movement Disorders Clinic at Tygerberg Hospital and via the Parkinson's Association of SA. Patient demographic and environmental data were recorded and associations with PD onset (EOPD v. LOPD) were analysed with a Pearson's Chi-squared test. The English- and Afrikaans-speaking (Afrikaner) white patients were analysed separately. Logistic regression analysis showed that ethnicity (p<0.001) and family history (p=0.004) were independently associated with AAO of PD. Average AAO was younger in black, coloured and Afrikaner patients than English-speaking white patients. A positive family history of PD, seen in 31.1% of LOPD patients, was associated with a younger AAO in the study population. These associations may be attributed to specific genetic and/or environmental risk factors that increase PD susceptibility and influence the clinical course of the disorder. More studies on PD in the unique SA populations are required to provide novel insights into mechanisms underlying this debilitating condition.

Association of PITX3 polymorphism with Parkinson's disease in Chinese patients

Objective To investigate the relationship between polymorphism in the PITX3 gene and hereditary susceptibility of Parkinson's disease(PD). Methods Three PITX3 single nucleotide polymorphisms (SNPs), including rs2281983, rs4919621 and rs3758549 were examined in 509 late-onset PD patients(LOPD), 290 early-onset PD(EOPD) and 494 healthy controls. Genotyping was carried out in all subjects using a ligase detection reaction(LDR). Results Allele and genotype frequencies did not differ between the 799 PD patients and 494 controls(P values of genotype were 0.494, 0.343, 0.951; P values of allele were 0.369, 0.297, 0.823), between 509 LOPD patients and 494 controls(P values of genotype were 0.522, 0.350, 0.630; P values of allele were 0.413, 0.328, 0.571), between 290 EOPD patients and 494 controls(P values of genotype were 0.499, 0.492, 0.552; P values of allele were 0.321, 0.301, 0.931), and between 509 LOPD and 290 EOPD patients(P values of genotype were 0.577, 0.710, 0.127; P values of allele were 0.346, 0.472, 0.077) for all three SNPs (rs2281983, rs4919621 and rs3758549). There were no association petween the three PITX3 SNPs and PD. Conclusion Three PITX3 SNPs do not contribute to the risk of developing PD in Chinese population. Key words: PITX3 gene; Late-onset Parkinson's disease; Early-onset Parkinson's disease; Single nucleotide polymorphisms

Long-term comparison of subthalamic nucleus stimulation between patients with young-onset and late-onset Parkinson’s disease

ObjectivesThe aim of this study was to compare the long-term effectiveness of subthalamic nucleus deep brain stimulation (STN-DBS) between patients with young-onset Parkinson’s disease (YOPD) and late-onset Parkinson’s disease (LOPD). Materials and MethodsTwenty-one YOPD patients with a mean age at onset of 32.8 ± 6.9 years and another 69 LOPD patients with a mean age at onset of 53.2 ± 6.9 years undergoing STN-DBS were followed. The mean durations of follow-up for those who were followed for more than 3 years were 57.22 ± 14.54 months in the YOPD group and 46.77 ± 13.84 months in the late onset group. ResultsMotor disabilities and activities of daily living in patients with LOPD and YOPD significantly improved after the operation. However, YOPD patients showed significantly less improvement in Unified Parkinson’s Disease Rating Scale Part II (p = 0.001) and Part III (p = 0.031), rigidity (p = 0.033), and axial (p = 0.046) scores than late onset patients more than 3 years after surgery. YOPD patients had higher scores for rigidity (p = 0.007) and bradykinesia (p = 0.044) than LOPD patients at the final post-surgery follow-up. Late onset PD patients had more postoperative hypophonia, whereas EOPD patients displayed more stimulation dyskinesia. The effects of STN-DBS on psychiatric complications and cerebral bleeding were similar in both groups. ConclusionYOPD patients and LOPD patients had similar benefits and risks from medication-related complications with STN-DBS. The YOPD group had relatively less improvement from acute deep brain stimulation than the LOPD group during long-term follow-up, which could possibly be explained by different disease evolutions and underlying pathophysiology in these two groups.

Genetic analysis of LRRK2 A419V variant in ethnic Chinese

Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most common causes of autosomal dominant and sporadic forms of Parkinson's disease (PD). The A419V variant has been suggested to be a potential risk variant but its role among Chinese is unclear. We genotyped LRRK2 A419V variant to investigate the association with risk of PD. A total of 1314 subjects comprising 729 patients with PD and 585 controls were genotyped. Twenty-two (3.0%) patients were heterozygous carriers for the A419V variant, and the frequency was higher compared with controls (0.7%, p = 0.003). The association was seen among the younger age group (early onset PD patients vs. controls: p = 0.0005), but was not significant among the older age group (late onset PD patients vs. controls: p = 0.17). We showed a significant association of LRRK2 A419V variant among early onset PD in the ethnic Han Chinese population but not among late onset PD. Further replication studies in additional Chinese and other Asian cohorts will be important to address its potential pathophysiologic role.

Analysis of the genotype of diacylglycerol kinase delta single-nucleotide polymorphisms in Parkinson disease in the Han Chinese population

Numerous Single-Nucleotide Polymorphisms (SNPs) of the Diacylglycerol Kinase Delta (DGKD) isoform 1 gene have been associated with Parkinson Disease (PD) in the genome-wide association studies of Caucasian population. This association has not been proven in the Han Chinese PD patients. This study included 376 unrelated Han Chinese PD patients from West China and 273 unrelated healthy controls from the same region. Five SNPs (rs2971859, rs1550532, rs2305539, rs2034762, and rs2242102) were genotyped using the Sequenom iPLEX Assay technology. No significant differences were observed in genotype frequencies and in the Minor Allele Frequency (MAF) in the five SNPs between PD patients and controls, early-onset PD and controls, late-onset PD and controls, and between early-onset and late-onset PD patients. The present study is the first to report on the lack of association of DGKD SNPs with PD in the Han Chinese population. More related studies involving larger numbers of participants are necessary to confirm the present finding.

PITX3 polymorphism is not associated with Parkinson's disease in a Chinese population

Several studies have indicated that three PITX3 single nucleotide polymorphisms (SNPs), rs2281983, rs4919621 and rs3758549, are likely to be associated with Parkinson's disease (PD) in Caucasians. Some studies also suggested an age-of-onset effect. We recently reported that allele and genotype frequencies did not differ between late-onset PD (LOPD) patients and controls for all three SNPs. To extend the analysis to early-onset PD (EOPD) patients, and to test whether an age-of-onset effect exists in Chinese, we genotyped these SNPs in 290 Chinese EOPD patients using a ligase detection reaction (LDR). For all three SNPs, allele and genotype frequencies did not differ between total PD patients and controls, between LOPD patients and controls, between EOPD patients and controls, or between LOPD and EOPD patients. Our results suggest that these PITX3 SNPs do not contribute to the risk of developing PD in EOPD or LOPD in Chinese.

Analysis of PARK2 gene exon rearrangements in Russian patients with sporadic Parkinson's disease

Deletions and duplications of single exons or exon groups account for a large proportion of the PARK2 gene mutations described in juvenile autosomal recessive Parkinson's disease (PD). We analyzed rearrangements in exons 1 to 12 of the PARK2 gene in Russian sporadic patients with early-onset PD (EOPD) and late-onset PD (LOPD). The frequency of EOPD and LOPD patients carrying these mutations was 12.4% and 3.8%, respectively. The most frequent rearrangements were detected in exons 3 and 4. The odds ratio for EOPD in individuals carrying PARK2 exon deletions and duplications was 13.95 (95% confidence interval [CI], 1.846-105.46; P = .0022). In addition, we found a correlation between exon rearrangements in PARK2 and the age at onset of PD, presence of dystonia, and symmetrical course of the disease. Exon rearrangements in the PARK2 gene play a significant role in the pathogenesis of sporadic PD in Russian patients.

HLA rs3129882 variant in Chinese Han patients with late-onset sporadic Parkinson disease

Recently, the rs3129882 variant in intron 1 of HLA-DRA was found to be associated with late-onset sporadic Parkinson disease (PD) in Americans of European ancestry. To evaluate whether the same variant is related to PD in Chinese population, we investigated late-onset sporadic PD patients of Chinese Han ethanicity in Mainland China. We found significant difference in genotypic and allele distribution between patients and control subjects (χ2=6.446, p=0.040 for genotypic distribution; χ2=5.762, p=0.016 for allele distribution), suggesting this variant is associated with late-onset sporadic PD in Chinese Han population.

Genetic variants of the PITX3 gene are not associated with late-onset sporadic Parkinson's disease in a Chinese population

PITX3 is a transcription factor which determines the survival of dopaminergic neurons in the substantia nigra, and is considered a candidate gene for Parkinson's disease (PD). Recent association studies indicated that three PITX3 single nucleotide polymorphisms (SNPs), including rs2281983, rs4919621, and rs3758549 are likely to be associated with PD. However, no similar associations in Chinese populations have been reported. To examine the nature of the association in Chinese individuals we analyzed DNA samples for these three PITX3 SNPs from 509 late-onset sporadic PD patients, and 494 healthy controls, using a ligase detection reaction (LDR). Results indicated that allele and genotype frequencies did not differ between patients and controls for all three SNPs, suggesting that these SNP sites do not contribute to the risk of developing PD in late-onset sporadic PD in this Chinese population.