APOLIPOPROTEIN-E AND ALZHEIMERS-DISEASE - ETHNIC VARIATION IN GENOTYPIC RISKS
APOLIPOPROTEIN-E AND ALZHEIMERS-DISEASE - ETHNIC VARIATION IN GENOTYPIC RISKS
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DOI：
10.1002/ana.410370217
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发表时间：
1995-02-01
影响因子：
11.2
通讯作者：
MAYEUX, R
中科院分区：
文献类型：
--
作者：
MAESTRE, G;OTTMAN, R;MAYEUX, R
载脂蛋白epsilon 4（类人猿epsilon 4）等位基因的存在显著增加了患阿尔茨海默病的风险。无论这是由于载脂蛋白epsilon 4蛋白的生物学效应，还是反映了与尚未确定的阿尔茨海默病易感基因的连锁不平衡，这一点至关重要。在曼哈顿北部的一项社区研究中，我们发现载脂蛋白4纯合子的非裔美国人、西班牙裔美国人和白人患阿尔茨海默病的风险增加了五倍。总的来说，阿尔茨海默病与载脂蛋白4杂合性之间的风险也增加了两倍，但与西班牙裔和白人相比，非裔美国人的这种关联要弱一些。相比之下，载脂蛋白2/ 3基因型与非裔美国人患阿尔茨海默病的风险增加了8倍有关，但与白人患病风险降低有关。在三个民族中，阿尔茨海默病与载脂蛋白E多态性之间的关联强度和类型的变异性不能完全用年龄差异来解释。各民族70岁及以下患者apoe*4等位基因频率明显高于对照组，反映载脂蛋白ε 4纯合子比例较高，但随着年龄的增长，这种差异逐渐减弱。非裔美国人和西班牙裔患者的apoe*2等位基因频率明显高于对照组，但白人患者的apoe*2等位基因频率明显高于对照组，但仅在70岁以后。虽然这些发现还有待证实，但它们表明，修饰基因或环境因素可能选择性地与非裔美国人的载脂蛋白ε 4相互作用，以削弱与阿尔茨海默病的关联，或者载脂蛋白E等位基因系统与附近尚未确定的阿尔茨海默病易感位点存在连锁不平衡。
The presence of the apolipoprotein epsilon 4 (ape epsilon 4) allele significantly increases the risk of Alzheimer's disease. Whether this is due to biological effects of the apo epsilon 4 protein or reflects linkage disequilibrium with an as yet unidentified Alzheimer's disease susceptibility gene is of critical importance. In a community study in northern Manhattan we found a fivefold increase in the risk of Alzheimer's disease among African-Americans, Hispanics, and whites homozygous for apo epsilon 4. Overall, the risk between Alzheimer's disease and apo epsilon 4 heterozygosity was also increased by twofold, but the association was somewhat weaker for African-Americans than for Hispanics and whites. In contrast, the apo epsilon 2/epsilon 3 genotype was associated with an eightfold increased risk of Alzheimer's disease in African-Americans but it was associated with reduced risk in whites. Variability in the strength and type of association between Alzheimer's disease and the apo E polymorphisms in the three ethnic groups could not be fully explained by age differences. The allelic frequency of apoe*4 was significantly higher in patients than control subjects in all ethnic groups at age 70 or younger, reflecting the higher proportion of apo epsilon 4 homozygotes, but this difference diminished with increasing age. The allelic frequency of apoe*2 for African-Americans and Hispanics, but not whites, was significantly higher in patients than control subjects, but only after age 70. Though these findings need confirmation, they suggest that modifier genes or environmental factors may interact selectively with apo epsilon 4 in African-Americans to weaken the association with Alzheimer's disease or that the apo E allelic system is in linkage disequilibrium with a nearby, as yet unidentified Alzheimer's disease susceptibility locus.