Interaction of TLR–IFN and HLA polymorphisms on susceptibility of chronic HBV infection in Southwest Han Chinese

Abstract

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. 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.

Massively parallel targeted resequencing reveals novel genetic variants associated with aspergillosis in paediatric patients with haematological malignancies

“…Conversely, two common SNPs in the TLR9 gene (promoter flanking rs187084 and rs352140 in the second exon) which showed significance for both allele and genotype frequencies (p < 0.05) in our analysis (Table II) did not reach the level of significance in an earlier association study on the risk of invasive aspergillosis among recipients of allogeneic haematopoietic cell transplants [19]. Nevertheless, many other studies have proved associations of rs187084 and rs352140 with numerous immune-related diseases, response to therapies, as well as bacterial and viral infections in populations of both Western and Eastern Eurasian ancestry [20,21,22,23,24,25]. It is also worth noting that the common rs4586 SNP, flanking the promoter of CCL2 gene, which appeared significant for genotype frequencies between our cases and controls (p = 0.0079, OR = 8.5, Table II), was recently found to be significantly correlated with anti-tumour immune reaction in Korean patients with colorectal cancer [26] and associated with the clinical outcome in Japanese individuals with locoregional gastric cancer [27].…”

Lack of association between human leukocyte antigen polymorphisms rs9277535 and rs7453920 and chronic hepatitis B in a Brazilian population

“…Several studies, especially analyzing Asian samples, found association between the SNP rs9277535 and chronic HBV infection (Kamatani et al, 2009;Lau et al, 2011;Mbarek et al, 2011;Png et al, 2011;Nishida et al, 2012;Yan et al, 2012;Kim et al, 2013;Al-Qahtani et al, 2014;Chang et al, 2014;Liao et al, 2014;Pan et al, 2014;He et al, 2015;Yu et al, 2015). Additionally, the study conducted by Thomas et al (2012) found an association between the SNP rs9277535 and the elimination rate of HBV in patients EuroAmerican and African-Americans (P = 0.0001).…”

“…In the study conducted by O'Brien et al (2011), the SNP rs9277535 was associated with a reduction in HLA-DPB1 gene expression in European patients. In Asian studies, the SNP rs7453920 was associated with the immune response to HBV (Mbarek et al, 2011;Al-Qahtani et al, 2014;Liao et al, 2014;He et al, 2015). However, no studies have associated this SNP in samples from other regions of the world.…”

IL‐1B rs16944 polymorphism is related to septic shock and death

“…However, there are some discrepancies as some studies did not find any genetic association of rs16944 with IL‐1β levels , infection or sepsis . In non‐European population, the rs16944 AA genotype has been related to lower risk of infection , and the GG genotype was associated with production of IL‐1β and higher risk of infection . Additionally, we performed an in silico analysis for evaluating the possible functional implication of rs16944 polymorphism using rSNABase (http://rsnp.psych.ac.cn/) .…”