Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression

Zhang Zhang; Yan Zhang; Minglei Shi; Bingyu Ye; Wenlong Shen; Ping Li; Lingyue Xing; Xiaopeng Zhang; Lihua Hou; Junjie Xu; Zhihu Zhao; Wei Chen

doi:10.3390/toxins8010001

Anthrax Susceptibility: Human Genetic Polymorphisms Modulating ANTXR2 Expression

Toxins (Basel). 2015 Dec 22;8(1):1. doi: 10.3390/toxins8010001.

Authors

Zhang Zhang¹, Yan Zhang², Minglei Shi³, Bingyu Ye⁴, Wenlong Shen⁵, Ping Li⁶, Lingyue Xing⁷, Xiaopeng Zhang⁸, Lihua Hou⁹, Junjie Xu¹⁰, Zhihu Zhao¹¹, Wei Chen¹²

Affiliations

¹ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
² Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
³ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁴ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁵ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁶ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁷ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁸ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
⁹ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
¹⁰ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
¹¹ Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].
¹² Beijing Institute of Biotechnology, No. 20, Dongdajie str., Fengtai District, Beijing 100071, China. [email protected].

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.

Keywords: ANTXR2; anthrax toxin; gene structure; gene transcription; genetic polymorphism.

MeSH terms

Antigens, Bacterial / toxicity*
Bacterial Toxins / toxicity*
Cell Line
Enhancer Elements, Genetic
Genetic Predisposition to Disease
Genetic Variation
HEK293 Cells
Humans
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Receptors, Peptide / genetics*

Substances

ANTXR2 protein, human
Antigens, Bacterial
Bacterial Toxins
Receptors, Peptide
anthrax toxin