Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression
Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no e...
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| Format: | Article |
| Language: | English |
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MDPI AG
2015-12-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/1/1 |
| _version_ | 1818038073149095936 |
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| author | Zhang Zhang Yan Zhang Minglei Shi Bingyu Ye Wenlong Shen Ping Li Lingyue Xing Xiaopeng Zhang Lihua Hou Junjie Xu Zhihu Zhao Wei Chen |
| author_facet | Zhang Zhang Yan Zhang Minglei Shi Bingyu Ye Wenlong Shen Ping Li Lingyue Xing Xiaopeng Zhang Lihua Hou Junjie Xu Zhihu Zhao Wei Chen |
| author_sort | Zhang Zhang |
| collection | DOAJ |
| description | Anthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility. |
| first_indexed | 2024-12-10T07:36:56Z |
| format | Article |
| id | doaj.art-e8b2598c3a24485d9dbfcfd8d5ed4b95 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-12-10T07:36:56Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-e8b2598c3a24485d9dbfcfd8d5ed4b952022-12-22T01:57:24ZengMDPI AGToxins2072-66512015-12-0181110.3390/toxins8010001toxins8010001Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 ExpressionZhang Zhang0Yan Zhang1Minglei Shi2Bingyu Ye3Wenlong Shen4Ping Li5Lingyue Xing6Xiaopeng Zhang7Lihua Hou8Junjie Xu9Zhihu Zhao10Wei Chen11Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaBeijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, ChinaAnthrax toxin causes anthrax pathogenesis and expression levels of ANTXR2 (anthrax toxin receptor 2) are strongly correlated with anthrax toxin susceptibility. Previous studies found that ANTXR2 transcript abundance varies considerably in individuals of different ethnic/geographical groups, but no eQTLs (expression quantitative trait loci) have been identified. By using 3C (chromatin conformation capture), CRISPR-mediated genomic deletion and dual-luciferase reporter assay, gene loci containing cis-regulatory elements of ANTXR2 were localized. Two SNPs (single nucleotide polymorphism) at the conserved CREB-binding motif, rs13140055 and rs80314910 in the promoter region of the gene, modulating ANTXR2 promoter activity were identified. Combining these two regulatory SNPs with a previously reported SNP, rs12647691, for the first time, a statistically significant correlation between human genetic variations and anthrax toxin sensitivity was observed. These findings further our understanding of human variability in ANTXR2 expression and anthrax toxin susceptibility.http://www.mdpi.com/2072-6651/8/1/1ANTXR2anthrax toxingene transcriptiongenetic polymorphismgene structure |
| spellingShingle | Zhang Zhang Yan Zhang Minglei Shi Bingyu Ye Wenlong Shen Ping Li Lingyue Xing Xiaopeng Zhang Lihua Hou Junjie Xu Zhihu Zhao Wei Chen Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression Toxins ANTXR2 anthrax toxin gene transcription genetic polymorphism gene structure |
| title | Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression |
| title_full | Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression |
| title_fullStr | Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression |
| title_full_unstemmed | Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression |
| title_short | Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression |
| title_sort | anthrax susceptibility human genetic polymorphisms modulating antxr2 expression |
| topic | ANTXR2 anthrax toxin gene transcription genetic polymorphism gene structure |
| url | http://www.mdpi.com/2072-6651/8/1/1 |
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