| Project/Area Number |
17590874
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Neurology
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
MIZUTA Ikuko Osaka University, Graduate School of Medicine, Research Fellow, 医学系研究科, 特別科学研究員 (80397760)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TODA Tatsushi Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (30262025)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Parkinson's disease / single nucleotide polymorphism / susceptibility gene / association study |
|---|
| Research Abstract |
Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder, with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case-control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case-control populations, we found that a SNP in α-synuclein (SNCA), rs7684318,showed the strongest association with PD (P=5.0x10^<-10>). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D'>0.9) spanning about 120 kb. A tight LD group (r^2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0x10^<-9>-1.7x10^<-11>). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated to the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.
|
