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Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity
Wang, Lin-Lin1,2; Li, Yong1; Zhou, Shu-Feng1
关键词Single Nucleotide Polymorphisms Non-synonymous Prediction Ethanol Toxicity
刊名TOXICOLOGY LETTERS
2009-06-01
DOI10.1016/j.toxlet.2009.02.007
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
WOS记录号WOS:000265958700006
项目编号30671760
资助机构National Natural Sciences Foundations of People&prime ; s Republic of China ; State Scholarship Fund of China
引用统计
被引频次:1[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50846
专题北京大学公共卫生学院
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
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GB/T 7714
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.
APA Wang, Lin-Lin,Li, Yong,&Zhou, Shu-Feng.(2009).Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity.TOXICOLOGY LETTERS,187(2),99-114.
MLA Wang, Lin-Lin,et al."Prediction of deleterious non-synonymous single nucleotide polymorphisms of genes related to ethanol-induced toxicity".TOXICOLOGY LETTERS 187.2(2009):99-114.
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