title: Interaction of TLR-IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese.
abstract: OBJECTIVE
  The toll-like receptor-interferon (TLR-IFN) signalling pathway plays a crucial role in HBV infection. Human leucocyte antigen (HLA) polymorphisms are associated with chronic HBV infection by genome wide association study (GWAS). We aimed to explore interaction between TLR-IFN and HLA gene polymorphisms in susceptibility of chronic HBV infection.
  
  
  METHODS
  In the Chinese Southwest Han population, 1191 chronic HBV infection patients and 273 HBV clearance were selected. A total of 39 single nucleotide polymorphism loci in 23 genes of the TLR-IFN pathway and four HLA polymorphism loci associated with chronic HBV infection identified by GWAS were selected for genotyping. SNPStats, QVALUE, and multifactor dimensionality reduction were used for statistical analysis.
  
  
  RESULTS
  A significant association was seen in several of the TLR-IFN pathway genes, TLR9 rs352140 (OR = 0.70, P = 0.0088), IL1B rs16944 (OR = 0.67, P = 0.016), IL12B rs3212227 (OR = 1.38, P = 0.021), IFNGR1 rs3799488 (OR = 1.48, P = 0.0048), IFNGR2 rs1059293 (OR = 0.27, P = 0.011), MX1 rs467960 (OR = 0.68, P = 0.022), as well as four loci in HLA, rs3077 (OR = 0.55, P < 0.0001), rs2856718 (OR = 0.60, P = 4e-04), rs9277535 (OR = 0.54, P < 0.0001) and rs7453920 (OR = 0.43, P < 0.0001). A synergistic relationship was seen between rs9277535 and rs16944 (0.13%), rs1143623 and rs6613 (0.10%). The combination of rs9277535 in HLA and rs16944 in IL1B was the best model to predict chronic HBV infection (testing accuracy = 0.6040, P = 0.0010, cross-validation consistency = 10/10).
  
  
  CONCLUSIONS
  TLR-IFN pathway gene polymorphisms are associated with chronic HBV infection. Interactions with polymorphisms in these genes may be one mechanism by which HLA polymorphisms influence susceptibility to chronic HBV infection, as specific single nucleotide polymorphism combinations are highly predictive of chronic HBV infection.
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|Liver Disease Diagnoses and Treatment Center of Chinese PLA, The 88th Hospital of Chinese PLA, Tai'an, Shandong Province, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Dengming
authors.initials: D
authors.lastname: He
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Tao
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Guo
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Maoshi
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Junqiu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Hongfei
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.|Sansure Biotech Inc., Changsha, Hunan Province, China.
authors.forename: Xinwu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Yan
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Institute of Infectious Disease, Southwest Hospital, Third Military Medical University, Chongqing, China.|The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000208:ethnology* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D017471:Receptors, Interferon / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D017471:Receptors, Interferon; D051193:Toll-Like Receptors
keywords: MDR; gene-gene interaction; hepatitis B virus; innate immune; polymorphism