| Project/Area Number |
16207020
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (A)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
生理人類学
|
|---|
| Research Institution | Osaka City University |
|---|
Principal Investigator |
SAEKI Shigeru Osaka City University, Graduate School of Human Life Science, Associate Professor (60211926)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SONE Yoshiaki Osaka City University, Graduate School of Human Life Science, Professor (60145802)
KIM Dong-Ho Osaka City University, Graduate School of Human Life Science, Lecturer (70326271)
FUKUMURA Tomoe Osaka City University, Graduate School of Human Life Science, Lecturer (80336792)
TAKAHASHI Sadao University of Fukui, Faculty of Medical Sciences, Lecturer (50303376)
松田 守弘 大阪大学, 生命機能研究科, 特任助手 (00362591)
|
|---|
| Project Period (FY) |
2004 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥49,660,000 (Direct Cost: ¥38,200,000、Indirect Cost: ¥11,460,000)
Fiscal Year 2006: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2005: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2004: ¥23,920,000 (Direct Cost: ¥18,400,000、Indirect Cost: ¥5,520,000)
|
|---|
| Keywords | lipoprotein receptor / lipid metabolism / エストロゲン / 骨代謝 / 骨粗鬆症 / 閉経 / リポ蛋白質受容体 |
|---|
| Research Abstract |
Alzheimer's disease (AD) is a progressive neurodegenerative disease of the central nervous system (CNS). The ε4 allele of the apolipoprotein E (apoE), APOEε4, has been shown to be a genetic susceptibility risk factor in both sporadic and late-onset familial AD. The apoE-containing lipoproteins secreted by astrocytes appear to be transported into other cells in the brain via receptor-mediated endocytosis. Therefore, the receptors for apoE-containing lipoproteins have been proposed to be associated with onset of AD. We previously isolated an apoE receptor 2 (ApoER2) that binds apoE-containing lipoproteins with high affinity. ApoER2 is predominantly expressed in the brain, and plays a significant role in development of the central nervous system (CNS) in collaboration with very low density lipoprotein receptor (VLDLR). We analyzed polymorphisms in the ApoER2 genes of Japanese sporadic AD patients and normal subjects. We found polymorphisms in length of CGG repeat (6-, 7- and 8-fold repeated alleles) located at 5'-UTR of the human ApoER2 gene. We also found polymorphisms in length of a CTG repeat (10- and 11-fold repeated alleles) in the signal sequence encoded by exon 1. This triplet repeat encodes a polyleucine stretch in the signal sequence of human ApoER2. We also found two variants in the ligand-binding domain that replace amino acids at positions 46 and 299 : c.374G>T : E46D in exon 2 and c.1132G>A : C299Y in exon 6. There were three other variants in the coding region that did not replace amino acids, 977C>T : R247R in exon 5. 1346C>T : D370D in exon 7. and c.3018G>T : P927P in exon 18. Allelic frequencies of the E46D variant were 52% and 53% in AD patients and normal subjects, respectively. There was one C299Y allele in AD patients and two in normal subjects, respectively.
|
