title: Genetic variants in IL12 influence both hepatitis B virus clearance and HBV-related hepatocellular carcinoma development in a Chinese male population.
abstract: IL12 plays a major role not only in inducing appropriate immune responses against viral infections (including HBV) but also in the antitumor immune response. This study was conducted to investigate the relationships of genetic variants in IL12 with hepatitis B virus (HBV) clearance and development of HBV-related hepatocellular carcinoma (HCC). We genotyped three single nucleotide polymorphisms (SNPs) of the IL12A (rs568406 and rs2243115) and IL12B (rs3212227) in 395 HBV-positive HCC patients, 293 persistent HBV carriers and 686 subjects with HBV natural clearance from southern China, using the improved multiplex ligase detection reaction (iMLDR) method. Logistic regression analysis adjusted for age, smoking, and alcohol consumption status showed that rs568408 variant genotypes were significantly associated with host HBV-related HCC risk when compared with persistent HBV carriers, and carriers of the GA + AA genotype decreased the HCC risk in comparison with GG carriers (adjusted OR = 0.53, 95 % CI 0.35-0.80, P = 0.002). No relationships between the rs2243115 and rs3212227 SNPs and HCC risk were observed (all P > 0.05). Besides, rs568408 showed an approaching significant effect on susceptibility to HBV persistent infection (adjusted OR = 1.34, 95 % CI 0.99-1.81, P = 0.057 in dominant genetic models). Furthermore, the TG haplotype was observed to be associated with a significantly increased risk of HBV-related HCC (OR = 1.42, 95 % CI 1.10-1.83, P = 0.006), while TA haplotype was associated with a decreased risk of HBV-related HCC (OR = 0.61, 95 % CI 0.45-0.83, P = 0.002). Our results reveal that the IL12A rs568408 variant may be a marker SNP for risk of both HBV clearance and HBV-related HCC development.
authors.affiliation: Department of chemotherapy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.|Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Tan
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Ziting
authors.initials: Z
authors.lastname: Yao
authors.affiliation: TalentCloud Information Technology Ltd, Nanning, Guangxi, 530021, China.
authors.forename: Shining
authors.initials: S
authors.lastname: Su
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Yuanliang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xian
authors.affiliation: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, 530021, China. zengnanmo@hotmail.com.
authors.forename: Zengnan
authors.initials: Z
authors.lastname: Mo
mesh_terms: D000328:Adult; D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D002681:China; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D018664:Interleukin-12
keywords: HBV-related HCC; IL12 gene; Persistent HBV infection