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学科主题: 公共卫生
题名:
Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity
作者: Wang, Lin-Lin1,2; Li, Yong1; Zhou, Shu-Feng1
关键词: Single nucleotide polymorphisms ; Non-synonymous ; Prediction ; Ethanol ; Toxicity
刊名: TOXICOLOGY LETTERS
发表日期: 2009-06-01
DOI: 10.1016/j.toxlet.2009.02.007
卷: 187, 期:2, 页:99-114
收录类别: SCI
文章类型: Review
WOS标题词: Science & Technology
类目[WOS]: Toxicology
研究领域[WOS]: Toxicology
关键词[WOS]: MU-OPIOID RECEPTOR ; MESSENGER-RNA EXPRESSION ; GENOME-WIDE ASSOCIATION ; SUBSTANCE USE DISORDERS ; DRUG-USE DISORDERS ; ALCOHOL-DEPENDENCE ; FRONTAL-CORTEX ; GABA(A) RECEPTOR ; CANDIDATE GENE ; LINKAGE DISEQUILIBRIUM
英文摘要:

Non-synonymous single nucleotide polymorphisms (nsSNPs) that cause amino acid changes are believed to have a large impact on protein function. it is important to distinguish those deleterious nsSNPs that affect protein function from those that are functionally neutral. Ethanol causes organ toxicity with involvement of a number of genes encoding functional proteins. We have identified 1509 alcohol-responsive genes after a systemic search of previous human studies, with 580 being up-regulated and 847 down-regulated. The samples for gene expression analysis of ethanol exposure are from the brain, liver, and cultured human cells. These genes mainly encode proteins involved in nucleic acid binding, transcription, and signal transduction. These ethanol-responsive genes also correlated with other biological pathways, such as angiogenesis, integrin signalling pathway, and inflammation. The number of nsSNPs in the 1509 validated alcohol-responsive genes was 9207. Using the PolyPhen and SIFT algorithms, 41.5% nsSNPs were predicted to be deleterious. These findings provide some insights into the molecular targets of ethanol-induced toxicity and how genetic mutation would affect the toxicity phenotype. A better understanding of the relationship between genotype and phenotype of nsSNPs of ethanol-responsive genes will provide useful hints for further research on alcohol-induced toxicity and potential therapy. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

语种: 英语
所属项目编号: 30671760
项目资助者: National Natural Sciences Foundations of People&prime ; s Republic of China ; State Scholarship Fund of China
WOS记录号: WOS:000265958700006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50846
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.RMIT Univ, WHO Collaborating Ctr Tradit Med, Discipline Chinese Med, Sch Hlth Sci, Bundoora, Vic 3083, Australia
2.Peking Univ, Dept Nutr & Food Hyg, Sch Publ Hlth, Inst Reprod & Child Hlth, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Lin-Lin,Li, Yong,Zhou, Shu-Feng. Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity[J]. TOXICOLOGY LETTERS,2009,187(2):99-114.
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