Role of Functional IFNL4,IFNLR1,IFNA, IFNAR2 Polymorphisms in Hepatitis B virus‐related liver disease in Han Chinese population

Abstract

Recent studies show that variants in some interferon genes together with interferon receptor genes are associated with the outcome of infectious diseases. We examined the association between the risk of hepatitis B virus (HBV)-related liver disease and the functional polymorphisms within IFNL4, IFNLR1, IFNA1, IFNA2, IFNA5 and IFNAR2 genes (14 loci in all) in a Han Chinese population. A total of 3128 people participated and were divided into 5 groups: healthy controls, natural clearance, chronic hepatitis B(CHB), liver cirrhosis and hepatocellular carcinoma (HCC). Significant associations were observed for 4 variants in IFNAR2, IFNLR1 with HBV infection, and IFNLR1-rs4649203 was associated with HBV recovery. Moreover, we demonstrated the clear relevance of 5 polymorphisms in IFNA1, IFNA2, IFNL4 with HCC. Three SNPs in IFNL4 gene may be important susceptible factors for the progression of HBV-related liver disease by trend chi-square test. The IFNL4 haplotype conformed by rs12971396_G, rs8113007_T and rs7248668A was more frequent in HCC than CHB and LC group. Three polymorphisms in the 5' region of the IFNL4 gene are associated with the progression of HBV-related liver disease. IFNA1- rs1831583 and IFNA2- rs649053 are associated with the development of HCC. IFNLR1- rs4649203, rs7525481 are predictors for HBV infection, and rs4649203 is a predictor of spontaneous clearance. IFNAR2 -rs1051393, rs12233338 may be predictive markers of HBV infection in the Chinese population.

Genetic variants of TLR9 Gene and Chronic Kidney Disease Susceptibility

“…Several research reported on SNPs of INFAR2 in hepatitis B virus infection, speci cally, there is a possibility that IFNAR2 polymorphisms is involved in chronic HBV infection susceptibility among Thailand population [34] and involved when determining IFN response and predictive marker of hepatitis B virus infection among Chinese Han population [35]. Ma et al [36] reported that the polymorphism of IFNAR2 (rs1051393 G > T) is missense changing from phenylalanine to valine. This SNP might be important in the risk of HBV infection by in uencing the expression of IFNAR2 protein on the surface of the cell resulting in anti-viral response and damaged signal transduction.…”

Review of Lambda Interferons in Hepatitis B Virus Infection: Outcomes and Therapeutic Strategies

“…Several studies in diverse ethnic and geographic cohorts comprised of healthy volunteers, patients who spontaneously cleared HBV infection, and patients who developed chronic HBV infection identified an association of IFNL polymorphisms with HBV infection outcomes [55][56][57]. However, multiple additional studies [58][59][60][61] and meta-analyses did not identify an association [62][63][64][65][66]. Most analyses examined SNPs within IFNL genes, but a case-control study in a Han Chinese cohort composed of 3128 patients (healthy controls, natural HBV clearance, or chronic HBV infection) found an association of IFNLR1 polymorphisms (rs7525481, rs4649203) with HBV susceptibility [60], which merits further evaluation in independent cohorts.…”

Structural integrity with functional plasticity: what type I IFN receptor polymorphisms reveal

“…1 [labelled “F”]). SNP rs2229207 is associated with an increased risk of a sustained virologic response (SVR) to hepatitis C, 62 whereas SNP rs1051393 is associated with an increased risk of MS, 43 hepatitis B infection, 63 hepatitis C chronicity, 64 and with severe pain in lung cancer patients 46 (Table 1). Both SNPs induce changes from large hydrophobic Phe residues to smaller Ser and Val residues, respectively, in a region of the signal peptide known for being enriched in hydrophobic residues 65 .…”