Hepatitis B virus genotypes, expression quantitative trait loci for ZNRD1-AS1 and their interactions in hepatocellular carcinoma.
Genetic variants in zinc ribbon domain-containing 1 antisense RNA 1 (ZNRD1-AS1) have been reported to be associated with development of hepatocellular carcinoma (HCC). We sought to determine the influences of ZNRD1-AS1 polymorphisms and their interactions with Hepatitis B virus (HBV) genotypes on the risk of HCC. In this study, we conducted a large population case-control study with 1,507 HBV-related HCC cases and 1,560 HBV persistent carriers. Three single-nucleotide polymorphisms (SNPs) in ZNRD1-AS1 (rs3757328, rs6940552 and rs9261204) were genotyped using a TaqMan allelic discrimination assay, and the HBV genotypes were identified by multiplex PCR. We found consistently significant associations between the ZNRD1-AS1 rs6940552 and rs9261204 SNPs with an increased risk of HCC (additive genetic model: adjusted OR = 1.16, 95% CI = 1.03-1.32 for rs6940552; adjusted OR =1.20, 95% CI = 1.06-1.35 for rs9261204) and found a borderline association between rs3757328 and HCC risk. Besides, we observed a dose-dependent relationship between increasing numbers of variant alleles of the SNPs and HCC risk (P for trend <0.001). Moreover, we observed a stronger combined effect of the three SNPs on HCC risk among the subjects infected with non-B genotype HBV (adjusted OR = 1.26, 95% CI = 1.05-1.50) compared with HBV B-related genotypes (adjusted OR = 0.89, 95% CI = 0.69-1.15; P= 0.029 for heterogeneity test). We also found that a multiplicative interaction between the variant alleles and the HBV genotype significantly affected HCC susceptibility (P = 0.030). Together, these results indicate that ZNRD1-AS1 may influence HCC risk accompanied by HBV genotypes.
Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zhenzhen
Z
Liu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
Ci
C
Song
Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital Affiliated with Nanjing Medical University, Nanjing, China.
Juan
J
Wen
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
Lu
L
Xu
Pathology Center and Department of Pathology, Soochow University, Suzhou, China.
Yao
Y
Liu
Qidong Liver Cancer Institute, The First People's Hospital of Qidong, Qidong, China.
Jian
J
Zhu
Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
Liguo
L
Zhu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
Zhibin
Z
Hu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center of Cancer Medicine, Nanjing Medical University, Nanjing, China.
Hongxia
H
Ma
Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Li
L
Liu
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012307:Risk Factors
D015395:Histocompatibility Antigens Class I; C112461:ZNRD1AS gene product, human
HBV genotype; HCC; eQTL; interaction; susceptibility