Heterogeneity among patients with Parkinson's disease: cluster analysis and genetic association.
The clinical heterogeneity of Parkinson's disease (PD) reveals the presence of several PD subtypes. The objectives of this study were to identify PD subtypes using cluster analysis (CA) and to determine the association between the subtypes and the polymorphisms in LRRK2 (G2385R and R1628P) and GBA (L444P) genes. A k-means CA of demographics, disease progression, motor and non-motor symptoms was performed from 1,510 Chinese PD patients from the Chinese National Consortium on Neurodegenerative Diseases. Pearson correlation analysis was performed to eliminate uninformative characteristics. Blood samples from 852 patients were obtained for genetic analysis of LRRK2 and GBA. Genotypic associations between various subtypes and genetic variants were examined using chi-square test. We identified four different subtypes: subtype 1 was non-tremor dominant (NTD, n=469; 31.1%); subtype 2 had a rapid disease progression with late onset (RDP-LO, n=67; 4.4%); subtype 3 had benign pure motor characteristics (BPM, n=778; 51.5%) without non-motor disturbances; and subtype 4 was tremor dominant with slow disease progression (TD-SP, n=196; 13.0%). Subtypes 1, 2, and 4 had similar mean age of onset. No associations were identified between polymorphisms in LRRK2 (R1628P) and GBA (L444P) genes and the four subtypes (P>0.05).
Center for Neurodegenerative disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, #6 Tian Tan Xi Li Street, Beijing 100050, China.
Ling-Yan
LY
Ma
Department of Neurobiology and Neurology, Xuanwu Hospital, Capital Medical University, #45 Changchun Street, Beijing 100053, China.; Key Laboratory on Neurodegenerative Disease of Ministry of Education and Key Laboratory on Parkinson's Disease of Beijing, #45 Changchun Street, Beijing 100053, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, #10 You'an Men Wai Xi Tou Tiao, Beijing 100069, China.
Piu
P
Chan
Department of Neurobiology and Neurology, Xuanwu Hospital, Capital Medical University, #45 Changchun Street, Beijing 100053, China.; Key Laboratory on Neurodegenerative Disease of Ministry of Education and Key Laboratory on Parkinson's Disease of Beijing, #45 Changchun Street, Beijing 100053, China.
Zhu-Qin
ZQ
Gu
Center for Neurodegenerative disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing 100050, China; China National Clinical Research Center for Neurological Diseases, #6 Tian Tan Xi Li Street, Beijing 100050, China.
Fang-Fei
FF
Li
Center for Neurodegenerative disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, #6 Tian Tan Xi Li Street, Beijing 100050, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, #10 You'an Men Wai Xi Tou Tiao, Beijing 100069, China; China National Clinical Research Center for Neurological Diseases, #6 Tian Tan Xi Li Street, Beijing 100050, China. Electronic address: happyft@sina.com.
Tao
T
Feng
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D016000:Cluster Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000145:classification / Q000235:genetics / Q000503:physiopathology; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D055815:Young Adult; D001617:beta-Glucosidase / Q000235:genetics
C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D001617:beta-Glucosidase
Cluster analysis; GBA; Genetic variants; LRRK2; Parkinson's disease; Polymorphisms