Rs4878104 contributes to Alzheimer’s disease risk and regulates DAPK1 gene expression

Hu, Yang; Liang, Cheng; Zhang, Ying; Bai, Wenming; Zhou, Wenyang; Wang, Tao; Han, Zhifa; Zong, Jian; Jin, Shuilin; Zhang, Jun; Jiang, Qinghua; Liu, Guiyou

doi:10.1007/s10072-017-2959-9

Cited by 25 publications

(14 citation statements)

References 53 publications

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“…All statistical tests for heterogeneity and meta-analysis were computed using R Package 1 . More detailed meta-analysis methods have been widely described in previous studies ( Liu et al, 2013b , 2017a , b , 2018 ; Hu et al, 2017a , b ).…”

Section: Methodsmentioning

confidence: 99%

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer’s Disease Risk

et al. 2018

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To determine the role of A disintegrin and metalloproteinase 10 (ADAM10) in genetic susceptibility to Alzheimer’s disease (AD) in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for the rs514049A/C and rs653765C/T polymorphisms in the ADAM10 promoter using the SNaPshot technique. We also examined the potential impact of these polymorphisms on the plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Additionally, a meta-analysis was performed using the present study and the largest GWAS from the International Genomics of Alzheimer’s Project (IGAP). No significant differences were found in the distributions of genotypes or alleles between AD patients and control subjects. However, age-at-onset stratification analysis revealed that there were significant differences in the genotypes (P = 0.015) and alleles (P = 0.006) of the rs653765 SNP. Furthermore, patients with the rs653765 CC genotype showed a lower ADAM10 level and a faster cognitive deterioration than those in patients with the CT/TT genotype in late-onset AD (LOAD), and the rs653765 CC polymorphism was able to regulate the production of the ADAM10 substrate sRAGE. In contrast, the rs514049 polymorphism was not statistically associated with AD. In the meta-analysis, we observed that both rs514049 (A allele vs. C allele, P = 0.002) and rs653765 (C allele vs. T allele, P = 0.004) were associated with AD risk. The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD.

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Section: Methodsmentioning

confidence: 99%

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer’s Disease Risk

et al. 2018

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“…During recent years, with the rapid advance of next-generation DNA sequencing, identify disease-related mutation from large data set and develop treatment become possible (Cheng et al, 2016a, 2018a,b). Genome-wide comparison studies (GWASs) have identified a significant amount of common genetic variants associated with complex traits and diseases (Welter et al, 2014; Hu et al, 2017a,b). Many previous studies have identified genes such as APOE (Mahoney-Sanchez et al, 2016; Liao et al, 2017) on chromosome 19.…”

Section: Introductionmentioning

confidence: 99%

Prediction of Alzheimer’s Disease-Associated Genes by Integration of GWAS Summary Data and Expression Data

2019

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Alzheimer’s disease (AD) is the most common cause of dementia. It is the fifth leading cause of death among elderly people. With high genetic heritability (79%), finding the disease’s causal genes is a crucial step in finding a treatment for AD. Following the International Genomics of Alzheimer’s Project (IGAP), many disease-associated genes have been identified; however, we do not have enough knowledge about how those disease-associated genes affect gene expression and disease-related pathways. We integrated GWAS summary data from IGAP and five different expression-level data by using the transcriptome-wide association study method and identified 15 disease-causal genes under strict multiple testing (α < 0.05), and four genes are newly identified. We identified an additional 29 potential disease-causal genes under a false discovery rate (α < 0.05), and 21 of them are newly identified. Many genes we identified are also associated with an autoimmune disorder.

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“…A Chinese research team validated these two gene variations (rs4877365 and rs4878104) with LOAD patients from the northern Han Chinese population in 2011, and the C allele of rs4878104 but not rs4877365 was recognized as a protective genetic factor of LOAD (odds ratio (OR): 0.75, p = 0.002), which provides the first evidence that DAPK1 allele-specific variants can influence the risk of developing LOAD in the Chinese population [82]. Although a much larger sample-based analysis showed a different conclusion from the previous one in that the rs4878104 variant is not significantly related to AD risk, it is significantly associated with AD susceptibility in the subgroup analysis [81].…”

Section: Dapk1mentioning

confidence: 65%

The Genetics of Alzheimer’s Disease in the Chinese Population

Gan

Zhang

Lee

2020

IJMS

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Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment. In China, the number of AD patients is growing rapidly, which poses a considerable burden on society and families. In recent years, through the advancement of genome-wide association studies, second-generation gene sequencing technology, and their application in AD genetic research, more genetic loci associated with the risk for AD have been discovered, including KCNJ15, TREM2, and GCH1, which provides new ideas for the etiology and treatment of AD. This review summarizes three early-onset AD causative genes (APP, PSEN1, and PSEN2) and some late-onset AD susceptibility genes and their mutation sites newly discovered in China, and briefly introduces the potential mechanisms of these genetic susceptibilities in the pathogenesis of AD, which would help in understanding the genetic mechanisms underlying this devastating disease.

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Rs4878104 contributes to Alzheimer’s disease risk and regulates DAPK1 gene expression

Cited by 25 publications

References 53 publications

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer’s Disease Risk

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer’s Disease Risk

Prediction of Alzheimer’s Disease-Associated Genes by Integration of GWAS Summary Data and Expression Data

The Genetics of Alzheimer’s Disease in the Chinese Population

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