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Aging and disease    2019, Vol. 10 Issue (1) : 94-101     DOI: 10.14336/AD.2018.0116
Orginal Article |
REST rs3796529 Genotype and Rate of Functional Deterioration in Alzheimer’s Disease
Poyin Huang1,2,3,4, Cheng-Sheng Chen5, Yuan-Han Yang6, Mei-Chuan Chou6, Ya-Hsuan Chang7, Chiou-Lian Lai1,*, Hsuan-Yu Chen3,7,8,*, Ching-Kuan Liu2,*
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.
3Ph.D. Program in Translational Medicine, Kaohsiung Medical University and Academia Sinica, Taiwan.
4Department of Neurology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
5Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan.
6Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan.
7Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
8Graduate institute of medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Recently, REST (RE1-silencing transcription factor) gene has been shown to be lost in Alzheimer’s disease (AD), and a missense minor REST allele rs3796529-T has been shown to reduce the rate of hippocampal volume loss. However, whether the REST 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.

Keywords genetics      biomarker      dementia      prognosis     
Corresponding Authors: Lai Chiou-Lian,Chen Hsuan-Yu,Liu Ching-Kuan   
About author:

These authors equally contributed to the work.

Issue Date: 02 October 2017
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Huang Poyin
Chen Cheng-Sheng
Yang Yuan-Han
Chou Mei-Chuan
Chang Ya-Hsuan
Lai Chiou-Lian
Chen Hsuan-Yu
Liu Ching-Kuan
Cite this article:   
Huang Poyin,Chen Cheng-Sheng,Yang Yuan-Han, et al. REST rs3796529 Genotype and Rate of Functional Deterioration in Alzheimer’s Disease[J]. Aging and disease, 2019, 10(1): 94-101.
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REST rs3796529Total ANT allele AN (%)Odds ratio (95% CI)p value
AD patients (n=584)1168430 (36.82%)
ExAC East Asian86423493 (40.42%)1.164 (1.026-1.321)0.018
1000 Genomes Han Chinese416145 (34.85%)0.918 (0.727-1.161)0.475
1000 Genomes East Asian1008380 (37.69%)1.039 (0.872-1.236)0.671
Taiwan Biobank Taiwanese1986402 (40.73%)1.180 (1.017-1.369)0.029
Table 1  Allele frequencies, allele numbers and odds ratios of rs3796529-T in patients with AD and East Asian general populations.
Figure 1.  Bar chart of allele frequencies of rs3796529-T in patients with AD and East Asian general populations.
AD patients (n=584)C/C (n=239)C/T (n=260)T/T (n=85)p value
Age (years)
Gender (Male)
Education (years)
APOE E4 carrier
Baseline CDR (0.5 or 1)
Baseline stages of AD0.140
Early (CDR=0.5 or 1)80.5% (n=178)75% (n=186)80.2% (n=65)
Middle (CDR=2)19% (n=42)24.6% (n=61)17.3% (n=14)
Late (CDR=3)0.5% (n=1)0.4% (n=1)2.5% (n=2)
Medication- Donepezil69.1%71.3%73.7%0.476
Table 2  Basic characteristics of the AD patients categorized by rs3796529 genotype.
Figure 2.  The 1-survival probability curve of the progression of AD for REST rs3796529 C/C was above that of REST rs3796529 C/T and T/T; p value according to the log-rank test.
VariableHazard ratio (95% CI)p value
Male0.868 (0.639-1.181)0.368
Age (years)0.983 (0.967-0.998)0.031
Education (years)1.016 (0.988-1.045)0.257
Baseline CDR score0.590 (0.451-0.773)<0.001
REST rs3796529 genotype (C/C as reference)
C/T0.793 (0.607-1.035)0.088
T/T0.593 (0.401-0.877)0.009
Table 3  Adjusted hazard ratios of risk factors in AD progression.
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