PMID- 25110835 OWN - NLM STAT- MEDLINE DCOM- 20160201 LR - 20220317 IS - 1098-2744 (Electronic) IS - 0899-1987 (Linking) VI - 54 IP - 11 DP - 2015 Nov TI - Expression quantitative trait loci in long non-coding RNA ZNRD1-AS1 influence both HBV infection and hepatocellular carcinoma development. PG - 1275-82 LID - 10.1002/mc.22200 [doi] AB - Zinc ribbon domain containing 1 (ZNRD1), cloned from human leukocyte antigen (HLA) region, may play integral roles in diverse processes including immune response against HBV infection and hepatocarcinogenesis. ZNRD1-AS1 (ZNRD1 antisense RNA 1) may be an important regulator of ZNRD1. By bioinformatics analyses, we identified that several single nucleotide polymorphisms (SNPs) in ZNRD1-AS1 may be expression quantitative trait loci (eQTLs) for ZNRD1. In this study, we hypothesized that these eQTLs SNPs in ZNRD1-AS1 may influence both chronic HBV infection and hepatocellular carcinoma (HCC) development. We designed a case-control study of 1300 HBV-positive HCC patients, 1344 HBV persistent carriers and, 1344 HBV natural clearance subjects to test the associations of three ZNRD1 eQTLs SNPs (rs3757328, rs6940552 and, rs9261204) in ZNRD1-AS1 with the risk of both chronic HBV infection and HCC. Logistic regression analyses in additive genetic model showed that variant alleles of all the three SNPs increased host HCC risk, whereas variant allele of rs3757328 was associated with HBV clearance. Moreover, the haplotype containing variant alleles of the three SNPs was significantly associated with both HCC development (adjusted OR = 1.18, 95% CI = 1.01-1.38, P = 0.035) and HBV clearance (adjusted OR = 0.83, 95% CI = 0.71-0.96, P = 0.013), when compared with the most frequent haplotype. In vitro experiments showed that ZNRD1 knockdown inhibited the expression of HBV mRNA and promoted proliferation of HepG2.2.15 cells. These findings suggest that ZNRD1 regulatory SNPs may be susceptibility makers for risk of both chronic HBV infection and HCC. CI - (c) 2014 Wiley Periodicals, Inc. FAU - Wen, Juan AU - Wen J AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Liu, Yao AU - Liu Y AD - Pathology Center and Department of Pathology, Soochow University, Suzhou, China. FAU - Liu, Jibin AU - Liu J AD - Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China. FAU - Liu, Li AU - Liu L AD - Digestive Endoscopy Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Song, Ci AU - Song C AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Han, Jing AU - Han J AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Zhu, Liguo AU - Zhu L AD - Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China. FAU - Wang, Cheng AU - Wang C AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Chen, Jianguo AU - Chen J AD - Qidong Liver Cancer Institute, Qidong, China. FAU - Zhai, Xiangjun AU - Zhai X AD - Department of Infection Diseases, Jiangsu Province Center for Disease Prevention and Control, Nanjing, China. FAU - Shen, Hongbin AU - Shen H AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. FAU - Hu, Zhibin AU - Hu Z AD - Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140811 PL - United States TA - Mol Carcinog JT - Molecular carcinogenesis JID - 8811105 RN - 0 (DNA-Binding Proteins) RN - 0 (POLR1H protein, human) RN - 0 (RNA, Antisense) RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Messenger) SB - IM MH - Alleles MH - Carcinoma, Hepatocellular/*genetics MH - Case-Control Studies MH - Cell Line, Tumor MH - DNA-Binding Proteins/*genetics MH - Female MH - Genetic Predisposition to Disease/genetics MH - Genotype MH - Hep G2 Cells MH - Hepatitis B virus/pathogenicity MH - Hepatitis B, Chronic/*genetics/virology MH - Humans MH - Liver Neoplasms/*genetics MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/genetics MH - Quantitative Trait Loci/*genetics MH - RNA, Antisense/*genetics MH - RNA, Long Noncoding/*genetics MH - RNA, Messenger/genetics OTO - NOTNLM OT - HCC OT - ZNRD1 OT - eQTLs OT - susceptibility EDAT- 2014/08/12 06:00 MHDA- 2016/02/02 06:00 CRDT- 2014/08/12 06:00 PHST- 2014/02/19 00:00 [received] PHST- 2014/06/05 00:00 [revised] PHST- 2014/06/07 00:00 [accepted] PHST- 2014/08/12 06:00 [entrez] PHST- 2014/08/12 06:00 [pubmed] PHST- 2016/02/02 06:00 [medline] AID - 10.1002/mc.22200 [doi] PST - ppublish SO - Mol Carcinog. 2015 Nov;54(11):1275-82. doi: 10.1002/mc.22200. Epub 2014 Aug 11.