DOSE-DEPENDENT ASSOCIATION OF APOLIPOPROTEIN-E ALLELE EPSILON-4 WITH LATE-ONSET, SPORADIC ALZHEIMERS-DISEASE

被引:73
作者
YOSHIZAWA, T
YAMAKAWAKOBAYASHI, K
KOMATSUZAKI, Y
ARINAMI, T
OGUNI, E
MIZUSAWA, H
SHOJI, S
HAMAGUCHI, H
机构
[1] UNIV TSUKUBA,INST CLIN MED,DEPT NEUROL,TSUKUBA,IBARAKI 305,JAPAN
[2] UNIV TSUKUBA,INST BASIC MED SCI,DEPT MED GENET,TSUKUBA,IBARAKI 305,JAPAN
关键词
D O I
10.1002/ana.410360416
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We examined the apolipoprotein E (apo E) genotypes in 47 patients with late-onset sporadic Alzheimer's disease (mean age at onset a standard deviation, 72.2 +/- 6.4 years), 8 with late-onset familial Alzheimer's disease (75.5 +/- 5.1 years), 18 with early-onset sporadic Alzheimer's disease (52.8 +/- 4.7 years), and 10 with early-onset familial Alzheimer's disease (52.0 +/- 6.8 years) in Japan and compared them with genotypes in control subjects. In late-onset sporadic Alzheimer's disease, apo E-epsilon 4 frequency increased significantly (epsilon 4 frequency: 0.34 vs 0.095 in controls, P < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E-epsilon 4, markedly increased with increasing dose of apo E-epsilon 4 gene (3[95% confidence interval, 2-6] in one dose; 43 [95% confidence interval, 12-154] in two doses). This study also suggested that apo E-epsilon 4 is associated with both late-onset (epsilon 4: 0.31) and early-onset familial Alzheimer's disease (epsilon 4: 0.35). In contrast, we found no association between apo E-epsilon 4 and early-onset sporadic Alzheimer's disease (epsilon 4: 0.08). These results indicate that the risk of developing late-onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E-epsilon 4, while apo E-epsilon 4 does not appear to be a major risk factor for early-onset sporadic Alzheimer's disease.
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页码:656 / 659
页数:4
相关论文
共 15 条
[11]   GENETIC-LINKAGE EVIDENCE FOR A FAMILIAL ALZHEIMERS-DISEASE LOCUS ON CHROMOSOME-14 [J].
SCHELLENBERG, GD ;
BIRD, TD ;
WIJSMAN, EM ;
ORR, HT ;
ANDERSON, L ;
NEMENS, E ;
WHITE, JA ;
BONNYCASTLE, L ;
WEBER, JL ;
ALONSO, ME ;
POTTER, H ;
HESTON, LL ;
MARTIN, GM .
SCIENCE, 1992, 258 (5082) :668-671
[12]   APOLIPOPROTEIN-E - HIGH-AVIDITY BINDING TO BETA-AMYLOID AND INCREASED FREQUENCY OF TYPE-4 ALLELE IN LATE-ONSET FAMILIAL ALZHEIMER-DISEASE [J].
STRITTMATTER, WJ ;
SAUNDERS, AM ;
SCHMECHEL, D ;
PERICAKVANCE, M ;
ENGHILD, J ;
SALVESEN, GS ;
ROSES, AD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (05) :1977-1981
[13]   APOLIPOPROTEIN-E GENOTYPING BY ONE-STAGE PCR [J].
WENHAM, PR ;
PRICE, WH ;
BLUNDELL, G .
LANCET, 1991, 337 (8750) :1158-1159
[14]   SCREENING OF THE MIS-SENSE MUTATION PRODUCING THE (717)VAL-]ILE SUBSTITUTION IN THE AMYLOID PRECURSOR PROTEIN IN JAPANESE FAMILIAL AND SPORADIC ALZHEIMERS-DISEASE [J].
YOSHIZAWA, T ;
KOMATSUZAKI, Y ;
IWAMOTO, H ;
MIZUSAWA, H ;
KANAZAWA, I .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1993, 117 (1-2) :12-15
[15]  
1993, LANCET, V342, P737