| Project/Area Number |
06670986
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Osaka Medical College |
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Principal Investigator |
YONEDA Hiroshi (1996) Osaka Medical College Neuropsychiatry, Associate Professor, 医学部, 助教授 (30140148)
野々村 安啓 (1994-1995) 大阪医科大学, 医学部, 助手 (70228344)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Toshiaki Osaka Medical College Neuropsychiatry, Professor, 医学部, 教授 (20084874)
米田 博 大阪医科大学, 医学部, 助教授 (30140148)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Alzheimer's disease / senile dementia / late onset / APOC-II / Association study / 痴呆性疾患 / 分子遺伝学 / アポリポタンパクCII / 相関 / 遺伝的異種性 / APO-C11 / 関連 / APOC-ll遺伝子 / イントロン / 多型 |
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| Research Abstract |
Pericak-Vance (1991) reported that late-onset familial Alzheimer's disease (AD) was linked to the long arm of chromosome 19. Schellenberg (1992) also reported that apolipoproteinC-II (ApoC-II) gene on the chromosome 19q13.2 region was linked with not early-onset but late-onset familial AD.APOC-II contained four exons and three introns and the 3rd intron was composed of minisatellites. It was found that a two-allele polymorphism in the 3rd intron, whose DNA sequence basis was a variation in the number of tandem repeats of a 40 base tau-like core sequence ; a 375 bp fragment corresponded to an allele with 7 repeat units (allele 1) while a 335bp fragment corresponded to an allele with 6 repeat units (allele 2). We investigated an association between APOC-II and sporadic late-onset AD.The subjects were 33 late-onset AD cases diagnosed according to the criteria of NINCDS-ADRDA and 92 normal controls. We extracted DNA from blood samples and amplified the intron 3 of the APOC-II by PCR.PCR products were electrophoresed in 3% agarose gel and stained by ethidium bromide. We detected the two bands : 375bp (allele 1) and 335bp (allele 2). Thses two bands suggest the existence of genotyper ; 1-1,1-2,2-2. The allele frequencies and the frequencies of genotypes of the controls were not significantly different from those expected from the Hardy-Weinberg equilibrium. The frequency of genotype 1-2 was significantly higher in the late-onset AD patients than in the controls. The frequency of allele 1 was higher in the late-onset patients than in the cotrols. A positve association between APOC-II and sporadic late-onset AD was found. This finding is consistent with earlier association studies with APOC-II polymorphism by Schellenberg (1992). The association we report here indicates that the DNA region with susceptibility to late-onset AD lies APOC-II at the chromosome 19q13.2.
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