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Genetic polymorphisms in the region of the interferon-λ genes ( IFNL ) associate with clearance of hepatitis C virus (HCV) infection. One of these polymorphisms,  IFNL4  rs368234815, determines loss or gain of function of the  IFNL4  gene by frameshift variation. The very same and a second one,  IFNL3  rs4803217, are supposed to impact the expression of  IFNL3 : while  IFNL4  rs368234815 is suggested to modulate  IFNL3  transcription,  IFNL3  rs4803217 is thought to alter  IFNL3  mRNA stability. The latter process is believed to be partially driven by an HCV-induced ectopic expression of myosin heavy chain genes 7 B  and  7  and their co-expressed microRNAs mir499 and mir208B. These ideas are evidenced by functional investigations on peripheral blood mononuclear and hepatoma cells in culture. Our study aimed at exploring  IFNL3  gene expression in clinical samples, i.e., in  ex vivo  derived liver tissue from patients with chronic hepatitis C (n = 57) and various other diseases (n = 56). By applying an assay designed to specifically quantify  IFNL3  and discriminating paralogous  IFNL2  transcripts,  IFNL3  mRNA expression was not found to differ significantly between chronic hepatitis C and control samples. Among patients with chronic HCV infection, moreover,  IFNL3  rs4803217 or  IFNL4  rs368234815 minor alleles did not associate with reduced  IFNL3  gene expression. Finally, myosin heavy chain genes 7 B  and  7  and corresponding microRNAs mir499 and mir208B were not found activated in liver in chronic HCV infection. Of note, detectability of  MYH7  mRNA related to the procedure of liver biopsy sampling, as tissue obtained by direct punctation of the liver during laparoscopic inspection was less likely to contain  MYH7  transcripts than samples acquired by percutaneous punctation. In conclusion, data on  ex vivo  derived liver tissue samples argue against an attenuating impact of  IFNL3  rs4803217 or  IFNL4  rs368234815 minor alleles on hepatic  IFNL3  gene expression  in vivo .

plos one

Hepatic Interferon-λ3 (IFNL3) Gene Expression Reveals Not to Be Attenuated in Non-Favorable IFNL3 rs4803217 or IFNL4 rs368234815 Minor Allele Carriers in Chronic Hepatitis C