Liao Yi-Chu, Lee Wei-Ju, Hwang Jeng-Ping, Wang Yen-Feng, Tsai Chia-Fen, Wang Pei-Ning, Wang Shuu-Jiun, Fuh Jong-Ling
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan.
Neurobiol Aging. 2014 Oct;35(10):2423.e7-2423.e13. doi: 10.1016/j.neurobiolaging.2014.05.009. Epub 2014 May 14.
The ATP-binding cassette, subfamily A, member 7 gene (ABCA7) was recently identified as a susceptible gene of Alzheimer's disease (AD) in the Caucasian population and African Americans. To test its genetic effect in the Han-Chinese population, 536 AD cases and 307 cognitive-intact, elder controls were genotyped for ABCA7 rs3764650 and apolipoprotein E (APOE) ε2/ε3/ε4 alleles. Global cognitive performance was assessed by the Mini-Mental State Examination in both AD patients and controls. For AD patients, comprehensive evaluation of each cognitive domain was further conducted as the following: (1) attention (forward and backward digit span); (2) memory (12-item word recall test); (3) executive function (category verbal fluency); (4) processing speed (Trail making test, part A); and (5) naming task (Boston naming test). ABCA7 rs3764650 was significantly associated with AD and the GG genotype carried a reduced risk for AD (odds ratio = 0.52, p = 0.0026). The association was further confirmed in 1802 population-based, healthy controls from Taiwan Biobank as a replicate (odds ratio = 0.70, p = 0.032). After adjustment of age, sex, and APOE ε4 allele, rs3764650 remained to be an independent predictor of AD (p = 0.001). The influence of ABCA7 was only evident in individuals without APOE ε4 alleles (p = 0.0004) but absent in ε4 carriers (p = 0.91). None of the cognitive tests was related to ABCA7 rs3764650 genotypes. The minor allele frequency and effect size of rs3764650 disclosed in the Han-Chinese population differed from those reported in the Caucasians and African Americans. Further studies were warranted to elucidate ABCA7's effect among different ethnic groups.
三磷酸腺苷结合盒转运体A亚家族第7成员基因（ABCA7）最近被确定为高加索人群和非裔美国人中阿尔茨海默病（AD）的一个易感基因。为了检测其在汉族人群中的遗传效应，对536例AD患者和307名认知功能正常的老年对照进行了ABCA7 rs3764650和载脂蛋白E（APOE）ε2/ε3/ε4等位基因的基因分型。通过简易精神状态检查表对AD患者和对照的整体认知表现进行评估。对于AD患者，对每个认知领域进行了如下进一步的综合评估：（1）注意力（顺背和倒背数字广度）；（2）记忆力（12项单词回忆测试）；（3）执行功能（类别言语流畅性）；（4）处理速度（连线测验A部分）；以及（5）命名任务（波士顿命名测试）。ABCA7 rs3764650与AD显著相关，GG基因型的AD发病风险降低（比值比=0.52，p=0.0026）。该关联在来自台湾生物银行的1802名基于人群的健康对照中作为重复验证得到进一步证实（比值比=0.70，p=0.032）。在调整年龄、性别和APOE ε4等位基因后，rs3764650仍然是AD的一个独立预测因子（p=0.001）。ABCA7的影响仅在没有APOE ε4等位基因的个体中明显（p=0.0004），而在ε4携带者中不存在（p=0.91）。没有一项认知测试与ABCA7 rs3764650基因型相关。汉族人群中rs3764650的次要等位基因频率和效应大小与高加索人和非裔美国人中报道的不同。有必要进行进一步研究以阐明ABCA7在不同种族群体中的作用。
