Genetic polymorphisms in ataxin-3 and liver cirrhosis risk related to aflatoxin B1.
Genetic polymorphisms in ataxin-3 and liver cirrhosis risk related to aflatoxin B1.
复制标题
ataxin-3基因多态性与黄曲霉毒素B1相关的肝硬化风险
DOI：
10.18632/oncotarget.24535
复制
发表时间：
2018-06-08
期刊：
影响因子：
--
通讯作者：
Long XD
中科院分区：
文献类型：
--
作者：
Wang XZ;Huang XY;Yao JG;Wang C;Xia Q;Long XD
共济失调蛋白-3（AT 3）的表达改变可以改变DNA修复能力，并在人类疾病中观察到。该基因在黄曲霉毒素B1（AFB 1）相关性肝硬化（LC）中的遗传多态性尚未阐明。我们进行了一项以医院为基础的病例对照研究，包括384例LC患者和851例无任何肝脏疾病的对照，以评估AT 3的264个多态性与AFB 1相关LC风险之间的关联。采用TaqMan-PCR或测序技术进行基因分型。通过筛选分析，我们发现了三个差异分布的SNP（rs 8021276，rs7158733和rs 10146249）;然而，只有rs 8021276多态性被进一步确定为改变LC的风险。与rs 8021276 A等位基因纯合子（rs 8021276-AA）相比，rs 8021276 G等位基因型（rs 8021276-AG或-GG）增加了LC的风险（OR分别为2.48和6.98; 95%CI分别为1.84-3.33和4.35-11.22）。在联合效应分析中还观察到风险基因型和AFB 1暴露状态之间的显著交互效应。此外，rs 8021276多态性还与肝硬化组织中AT 3 mRNA表达下调和AFB 1-DNA加合物增加有关。这些结果表明，AT 3基因多态性可能是AFB 1相关LC的危险生物标志物，rs 8021276是一个潜在的候选者。
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. 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. 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. These results suggest AT3 polymorphisms may be risk biomarkers of AFB1-related LC, and rs8021276 is a potential candidate.