Immunol Invest. 2019 Mar 25:1-14. doi: 10.1080/08820139.2019.1567532. [Epub ahead of print]
Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.
Li N1, Fan X1, Wang X1, Deng H1, Zhang K1, Zhang X1, Han Q1, Lv Y2,3, Liu Z1,3.
Author information
1
a Department of Infectious Diseases , First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.
2
b Department of Hepatobiliary Surgery , First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.
3
c Institute of Advanced Surgical Technology and Engineering , Xi'an Jiaotong University , Xi'an , Shaanxi , People's Republic of China.
Abstract
BACKGROUND:
Despite the identification of autophagy-related protein 5 (ATG5) as a molecule involved in the activated autophagy machinery during hepatitis B virus (HBV) infection and hepatocarcinogenesis, the consequences of ATG5 mutation carriage for patients with chronic HBV infection remain unclear. This study examined the association of ATG5 polymorphisms with HBV-related diseases including hepatocellular carcinoma (HCC).
PATIENTS AND METHODS:
Two functionally relevant polymorphisms ATG5 rs573775 and rs510432 were genotyped by ligase detection reaction-polymerase chain reaction in 403 patients with chronic HBV infection (171 chronic hepatitis, 119 cirrhosis and 113 HCC) and 196 healthy controls. Univariate and multivariate logistic regression was performed to evaluate factors associated with HCC.
RESULTS:
The rs573775 genotype and allele frequencies had no significant differences between patients with different clinical diseases. However, HCC patients had significantly higher frequency of rs510432 genotype AA (odds ratio [OR] 2.185, 95% confidence interval [CI] 1.042-4.581, P = 0.037, P value by Bonferroni correction [Pc] = 0.074) and allele A (OR 1.435, 95% CI 1.023-2.013, Pc = 0.036) than chronic hepatitis patients. In multivariate analyses, rs510432 allele A-containing genotypes (AA+GA) were independently associated with cirrhosis in comparison to chronic hepatitis (OR 1.927, 95%CI 1.011-3.017, P = 0.032). The rs510432 genotypes AA+GA were also independently associated with HCC in comparison to chronic hepatitis (OR 2.583, 95% CI 1.025-3.911, P = 0.006) or chronic HBV infection without HCC (OR 2.632, 95% CI 1.067-3.482, P = 0.032).
CONCLUSION:
These results indicate that rs510432 genotypes AA+GA are associated with disease progression and HCC risk in chronic HBV infection, providing novel evidence for a role of ATG5 in the pathogenesis of HBV-related HCC.
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