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.