Huang Poyin, Chen Cheng-Sheng, Yang Yuan-Han, Chou Mei-Chuan, Chang Ya-Hsuan, Lai Chiou-Lian, Chen Hsuan-Yu, Liu Ching-Kuan
1Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
2Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Aging Dis. 2019 Feb 1;10(1):94-101. doi: 10.14336/AD.2018.0116. eCollection 2019 Feb.
Recently, (RE1-silencing transcription factor) gene has been shown to be lost in Alzheimer's disease (AD), and a missense minor allele rs3796529-T has been shown to reduce the rate of hippocampal volume loss. However, whether the rs3796529 genotype is associated with the rate of functional deterioration in AD is unknown. A total of 584 blood samples from Taiwanese patients with AD were collected from January 2002 to December 2013. The diagnosis of AD was based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria. The allele frequency of rs3796529-T was compared between the AD cohort and 993 individuals from the general population in Taiwan. Kaplan-Meier analysis, the log rank test and a multivariate Cox model were then used to evaluate the association between rs3796529-T and functional deterioration in the AD cohort. The allele frequency of rs3796529-T was significantly lower in the AD cohort compared to the general population cohort (36.82% vs. 40.73%, p=0.029). Kaplan-Meier analysis and the log rank test showed that the AD patients carrying the rs3796529 T/T genotype had a longer progression-free survival than those with the C/C genotype (p=0.012). In multivariate analysis, the rs3796529 T/T genotype (adjusted HR=0.593, 95% CI: 0.401-0.877, p=0.009) was an independent protective factor for functional deterioration. The rs3796529 T/T genotype was associated with slower functional deterioration in patients with AD. This finding may lead to a to better understanding of the molecular pathways involved, and prompt further development of novel biomarkers to monitor AD.
最近，（RE1沉默转录因子）基因已被证实在阿尔茨海默病（AD）中缺失，并且一个错义次要等位基因rs3796529-T已被证实在降低海马体积丢失率方面有作用。然而，rs3796529基因型是否与AD患者功能衰退的速率相关尚不清楚。2002年1月至2013年12月期间，共收集了584例来自台湾AD患者的血样。AD的诊断基于美国国立神经疾病与中风研究所及阿尔茨海默病及相关疾病协会的标准。比较了AD队列与来自台湾普通人群的993名个体之间rs3796529-T的等位基因频率。随后采用Kaplan-Meier分析、对数秩检验和多变量Cox模型来评估rs3796529-T与AD队列中功能衰退之间的关联。与普通人群队列相比，AD队列中rs3796529-T的等位基因频率显著更低（36.82%对40.73%，p=0.029）。Kaplan-Meier分析和对数秩检验表明，携带rs3796529 T/T基因型的AD患者无进展生存期长于携带C/C基因型的患者（p=0.012）。在多变量分析中，rs3796529 T/T基因型（校正风险比=0.593，95%置信区间：0.401-0.877，p=0.009）是功能衰退的独立保护因素。rs3796529 T/T基因型与AD患者功能衰退较慢有关。这一发现可能有助于更好地理解其中涉及的分子途径，并促使进一步开发用于监测AD的新型生物标志物。
