Dataset Information

Genetic variations in chromodomain helicase DNA-binding protein 5, gene-environment interactions and risk of sporadic Alzheimer's disease in Chinese population.

ABSTRACT: CHD5 is an essential factor for neuronal differentiation and neurodegenerative diseases. Here, the targeted next generation sequencing and TaqMan genotyping technologies were carried out for CHD5 gene in a two-staged case-control study in Chinese population. The genetic statistics and gene-environment interactions were analyzed to find certain risk factors of Alzheimer's disease. We found intronic rs11121295 was associated with the risk of Alzheimer's disease at both stages including combined cohorts. This risk effect presented consistently significant associations with the alcoholic subgroups at both all stages in the stratified analysis. The gene-environment interactions further supported the above findings. Our study highlighted the potential role of CHD5 variants in conferring susceptibility to sporadic Alzheimer's disease, especially modified its risk by alcoholic intake.

SUBMITTER: Zhu X

PROVIDER: S-EPMC5982770 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Genetic variations <i>in chromodomain helicase DNA-binding protein 5</i>, gene-environment interactions and risk of sporadic Alzheimer's disease in Chinese population.

Zhu Xiao X Yu Haibing H Xiao Qin Q Ke Jianhao J Li Hongmei H Chen Zhihong Z Ding Hongrong H Leng Shuilong S Huang Yongmei Y Zhan Jingting J Lei Jinli J Fan Wenguo W Luo Hui H

Oncotarget 20180518 38

CHD5 is an essential factor for neuronal differentiation and neurodegenerative diseases. Here, the targeted next generation sequencing and TaqMan genotyping technologies were carried out for <i>CHD5</i> gene in a two-staged case-control study in Chinese population. The genetic statistics and gene-environment interactions were analyzed to find certain risk factors of Alzheimer's disease. We found intronic rs11121295 was associated with the risk of Alzheimer's disease at both stages including comb ...[more]

PMID: 29861839

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Project description:Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in patients with this disease. However, information on CHD4 mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking. The present work examines mutations in CHD4 reported in patients with breast cancer and included in public databases and attempts to identify their roles in its development. The databases revealed 81 point mutations across different types of breast cancer (19 of which also appeared in endometrial, intestinal, nervous system, kidney, and lymphoid organ cancers). 71.6% of the detected mutations were missense mutations, 13.6% were silent, and 6.2% nonsense. Over 50% affected conserved residues of the ATPase motor (ATPase and helicase domains), and domains of unknown function in the C-terminal region. Thirty one mutations were classified in the databases as either 'deleterious', 'probably/possibly damaging' or as 'high/medium pathogenic'; another five nonsense and one splice-site variant were predicted to produce potentially harmful truncated proteins. Eight of the 81 mutations were categorized as putative driver mutations and have been found in other cancer types. Some mutations seem to influence ATPase and DNA translocation activities (R1162W), while others may alter protein stability (R877Q/H, R975H) or disrupt DNA binding and protein activity (R572*, X34_splice) suggesting CHD4 function may be affected. In vivo tumorigenecity studies in endometrial cancer have revealed R975H and R1162W as mutations that lead to CHD4 loss-of-function. Our study provides insight into the molecular mechanism whereby CHD4, and some of its mutants could play a role in breast cancer and suggest important implications for the biological comprehension and prognosis of breast cancer, identifying CHD4 as a novel therapeutic target for BC patients.

Dataset Information

Genetic variations in chromodomain helicase DNA-binding protein 5, gene-environment interactions and risk of sporadic Alzheimer's disease in Chinese population.

Publications

Genetic variations <i>in chromodomain helicase DNA-binding protein 5</i>, gene-environment interactions and risk of sporadic Alzheimer's disease in Chinese population.

Similar Datasets

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