Abstract
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.
Highlights
Alzheimer’s disease (AD) is the most common form of developed countries, AD is the only disease that cannot be dementia worldwide, and it is the leading cause of death prevented, cured or even slowed [1]
Genetics play a role in susceptibility to all common human diseases including AD, and so identifying genetic biomarkers including single nucleotide polymorphisms (SNPs) and epigenetic markers for AD may facilitate classification of individuals according to drug response, disease progression and prognosis, thereby improving therapeutic outcomes and allowing for personalized management [3]
The aim of this study was to identify whether the REST rs3796529 genotype is associated with the rate of functional deterioration in AD, which could be useful in clinical practice
Summary
Alzheimer’s disease (AD) is the most common form of developed countries, AD is the only disease that cannot be dementia worldwide, and it is the leading cause of death prevented, cured or even slowed [1]. Genetics play a role in susceptibility to all common human diseases including AD, and so identifying genetic biomarkers including single nucleotide polymorphisms (SNPs) and epigenetic markers for AD may facilitate classification of individuals according to drug response, disease progression and prognosis, thereby improving therapeutic outcomes and allowing for personalized management [3] This concept of “precision medicine” has emerged in recent years as an approach for disease prevention and management that is personalized to an individual’s specific pattern of genetic variability, environment and lifestyle factors [4]. Other studies using a large scale GWAS dataset found that the association between the REST rs3796529 allele and susceptibility to AD was not significant in a European population, and that it did not significantly influence human subcortical brain structures [8,9,10]. The aim of this study was to identify whether the REST rs3796529 genotype is associated with the rate of functional deterioration in AD, which could be useful in clinical practice
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