Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Genetic polymorphisms in ataxin-3 and liver cirrhosis risk related to aflatoxin B1

Xing-Zhizi Wang _, Xiao-Ying Huang, Jin-Guang Yao, Chao Wang, Qiang Xia and Xi-Dai Long

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Oncotarget. 2018; 9:27321-27332. https://doi.org/10.18632/oncotarget.24535

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Abstract

Xing-Zhizi Wang1,*, Xiao-Ying Huang1,*, Jin-Guang Yao1,*, Chao Wang2, Qiang Xia3 and Xi-Dai Long1,3,4

1Department of Pathology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China

2Department of Digestive Medicine, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China

3Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

4Guangxi Clinic Research Center of Hepatobiliary Diseases, Baise 533000, China

*These authors contributed equally to this work

Correspondence to:

Xi-Dai Long, email: sjtulongxd@263.net

Keywords: ataxin-3; polymorphism; liver cirrhosis; aflatoxin B1; Gerotarget

Received: August 02, 2017     Accepted: November 07, 2017     Epub: February 19, 2018     Published: June 08, 2018

ABSTRACT

Background: Altered expression of ataxin-3 (AT3) can modify DNA repair capacity and is observed in human diseases. The genetic polymorphisms of this gene in aflatoxin B1 (AFB1)–related liver cirrhosis (LC) have not yet been elucidated.

Materials and Methods: We conducted a hospital-based case–control study, including 384 patients with LC and 851 controls without any liver diseases, to assess the association between 264 polymorphisms in AT3 and AFB1-related LC risk. Genotype were tested using TaqMan-PCR or sequencing technique.

Results: We found three differentially distributed SNPs (rs8021276, rs7158733, and rs10146249) via the screening analysis; however, only rs8021276 polymorphism was further identified to modify the risk of LC. Compared with the homozygote of rs8021276 A alleles (rs8021276-AA), the genotypes of rs8021276 G alleles (rs8021276-AG or -GG) increased LC risk (OR: 2.48 and 6.98; 95% CI: 1.84–3.33 and 4.35–11.22, respectively). Significant interactive effects between risk genotypes and AFB1 exposure status were also observed in the joint effects analysis. Additionally, rs8021276 polymorphism was also associated with down-regulation of AT3 mRNA expression and increasing AFB1-DNA adducts in liver tissues with cirrhosis.

Conclusions: These results suggest AT3 polymorphisms may be risk biomarkers of AFB1-related LC, and rs8021276 is a potential candidate.


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