Yang J D, Feng G Y, Zhang J, Cheung J, St Clair D, He L, Ichimura Keiichi
Shanghai Research Centre of Life Sciences, Chinese Academy of Sciences, Shanghai, China.
Neurosci Lett. 2003 Oct 16;350(1):25-8. doi: 10.1016/s0304-3940(03)00815-2.
Polymorphisms at positions -491, -427 and -219 in the promoter region of the Apolipoprotein E APOE gene have been variously reported to confer an increased risk of developing Alzheimer's disease (AD) independent of the effect of epsilon 2, 3 or 4 alleles in exon 4. In order to assess APOE promoter polymorphisms as independent risk factors in AD we have compared results in 183 definite or probable AD cases with 133 controls. We assayed markers at sites -491, -427, -219, and +113 in APOE gene and a polymorphic Hha1 site in the nearby APOC1 gene. We found that APOE promoter polymorphisms and APOC1 insertion alleles were significantly associated with AD. However, after stratification for epsilon 4 allele, only the A allele at -491 in APOE remained significantly associated with AD. The effects of the other markers depended almost entirely upon linkage disequilibrium with epsilon 4 allele, and only trends remained when cases and controls were stratified for the presence or absence of epsilon 4 allele. This occurred irrespective of whether markers were examined separately or together as haplotypes. So in the Chinese population only APOE -491 promoter alleles confer significant risk of AD independent of epsilon 4 status.
载脂蛋白E（APOE）基因启动子区域-491、-427和-219位点的多态性，有不同报道称其会增加患阿尔茨海默病（AD）的风险，且与第4外显子中ε2、ε3或ε4等位基因的作用无关。为了评估APOE启动子多态性作为AD独立风险因素的情况，我们比较了183例确诊或疑似AD病例与133例对照的结果。我们检测了APOE基因中-491、-427、-219和+113位点的标记以及附近APOC1基因中的一个多态性Hha1位点。我们发现APOE启动子多态性和APOC1插入等位基因与AD显著相关。然而，在按ε4等位基因分层后，只有APOE基因中-491位点的A等位基因仍与AD显著相关。其他标记的作用几乎完全取决于与ε4等位基因的连锁不平衡，当病例和对照按是否存在ε4等位基因分层时，仅存在趋势性关联。无论标记是单独检测还是作为单倍型一起检测，均是如此。所以在中国人群中，只有APOE -491启动子等位基因会独立于ε4状态而显著增加患AD的风险。
