title: Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression.
abstract: 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.
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. zzhnng@yeah.net.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. zany1983@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. shiml79@126.com.
authors.forename: Minglei
authors.initials: M
authors.lastname: Shi
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. byy0804@gmail.com.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Ye
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. shenwl1988@gmail.com.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Shen
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. lipingtry@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. xinglyinfo@163.com.
authors.forename: Lingyue
authors.initials: L
authors.lastname: Xing
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. zxp8565@aliyun.com.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. houlihua@sina.com.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hou
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. xujunjie@sina.com.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. zhaozh@nic.bmi.ac.cn.
authors.forename: Zhihu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. cw0730@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000942:Antigens, Bacterial / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D057809:HEK293 Cells; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018000:Receptors, Peptide / Q000235:genetics*
chemical_list: C447150:ANTXR2 protein, human; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin
keywords: ANTXR2; anthrax toxin; gene structure; gene transcription; genetic polymorphism