Graff-Radford Neill R, Green Robert C, Go Rodney C P, Hutton Michael L, Edeki Timi, Bachman David, Adamson Jennifer L, Griffith Patrick, Willis Floyd B, Williams Mary, Hipps Yvonne, Haines Jonathan L, Cupples L Adrienne, Farrer Lindsay A
Genetics Program L-320, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA.
Arch Neurol. 2002 Apr;59(4):594-600. doi: 10.1001/archneur.59.4.594.
The association between Alzheimer disease (AD) and genotypes at the apolipoprotein E (APOE) locus has been confirmed in numerous populations worldwide, but appears to be inconsistent in African American subjects.
To investigate the association between APOE genotypes and AD in elderly African American subjects.
Clinic-based, multicenter case-control study and a family study.
A total of 338 African American probands meeting criteria for probable or definite AD, 301 cognitively healthy, elderly unrelated control subjects (spouses and community volunteers), and 108 siblings of 88 AD probands.
Odds of AD according to APOE genotype.
Compared with individuals with the APOEepsilon3/epsilon3, the odds of having AD were significantly increased among those with 1 or more copies of the epsilon4 allele; the odds ratio (OR) for the epsilon3/epsilon4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the epsilon4/epsilon4 genotype was 10.5 (95% CI, 5.1-21.8). These risks decreased substantially after 68 years of age. The risk for AD was lower among individuals with the epsilon2/epsilon3 genotype (OR, 0.41; 95% CI, 0.22-0.79). The patterns of association were similar in men and women. These results obtained from comparisons of unrelated AD patients and controls were bolstered by results of analysis of family data that showed preferential transmission of the epsilon4 allele to demented siblings (P<<.001) and of the epsilon2 allele to nondemented siblings (P=.005).
The presence of 1 or 2 epsilon4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the epsilon4 allele and the apparent protective effect of the epsilon2 allele are similar to patterns observed in white subjects.
载脂蛋白E（APOE）基因座的基因型与阿尔茨海默病（AD）之间的关联在全球众多人群中已得到证实，但在非裔美国受试者中似乎并不一致。
研究老年非裔美国受试者中APOE基因型与AD之间的关联。
基于诊所的多中心病例对照研究和家系研究。
共有338名符合可能或确诊AD标准的非裔美国先证者、301名认知健康的老年非亲属对照受试者（配偶和社区志愿者）以及88名AD先证者的108名兄弟姐妹。
根据APOE基因型得出的患AD的几率。
与携带APOEε3/ε3的个体相比，携带1个或更多ε4等位基因拷贝的个体患AD的几率显著增加；ε3/ε4基因型的优势比（OR）为2.6（95%置信区间[CI]，1.8 - 3.7），ε4/ε4基因型的OR为10.5（95% CI，5.1 - 21.8）。68岁以后这些风险大幅降低。携带ε2/ε3基因型的个体患AD的风险较低（OR，0.41；95% CI，0.22 - 0.79）。男性和女性的关联模式相似。通过对非亲属AD患者和对照进行比较得出的这些结果，得到了家系数据分析结果的支持，家系数据分析显示ε4等位基因优先传递给患痴呆的兄弟姐妹（P <<.001），而ε2等位基因优先传递给未患痴呆的兄弟姐妹（P =.005）。
存在1个或2个ε4等位基因是非洲裔美国受试者患AD风险的一个决定因素。与ε4等位基因相关的与年龄相关的衰退风险以及ε2等位基因的明显保护作用与在白人受试者中观察到的模式相似。
