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Interaction of TLR – IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese
Author(s) -
He Dengming,
Tao Shiqi,
Guo Shimin,
Li Maoshi,
Wu Junqiu,
Huang Hongfei,
Guo Xinwu,
Yan Guohua,
Zhu Peng,
Wang Yuming
Publication year - 2015
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12756
Subject(s) - single nucleotide polymorphism , genotyping , immunology , human leukocyte antigen , genome wide association study , biology , allele , gene , genotype , antigen , genetics
Background & Aims 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. SNPS tats, QVALUE , and multifactor dimensionality reduction were used for statistical analysis. Results A significant association was seen in several of the TLR – IFN pathway genes, TLR 9 rs352140 ( OR = 0.70, P = 0.0088), IL 1B rs16944 ( OR = 0.67, P = 0.016), IL 12B rs3212227 ( OR = 1.38, P = 0.021), IFNGR 1 rs3799488 ( OR = 1.48, P = 0.0048), IFNGR 2 rs1059293 ( OR = 0.27, P = 0.011), MX 1 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 IL 1B 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.