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Javier Brahm, Alvaro Urzúa, Jaime Poniachik, Dante D Cáceres, Laura Carreño, Mauricio Venegas
BACKGROUND: Host genetic predispositions may be important determinants of liver fibrosis in patients with chronic hepatitis C (CHC). The association between Interferon-L 4 (IFNL4) rs12979860 C>T polymorphism and risk of liver fibrosis in CHC is contradictory. AIM: To evaluate the impact of IFNL4 rs12979860 polymorphism on the risk of fibrosis in patients with CHC. MATERIAL AND METHODS: One hundred fifty patients with CHC aged 50 ± 11 years (89 females) were genotyped for IFNL4 rs12979860 using real time PCR...
July 2018: Revista Médica de Chile
Tsion Zewdu Minas, Wei Tang, Cheryl J Smith, Olusegun O Onabajo, Adeola Obajemu, Tiffany H Dorsey, Symone V Jordan, Obadi M Obadi, Bríd M Ryan, Ludmila Prokunina-Olsson, Christopher A Loffredo, Stefan Ambs
Sexually transmitted infections can reach the prostate gland where their harmful effects are mediated by innate immunity, including interferons. Humans are polymorphic for the germline dinucleotide variant, rs368234815-TT/ΔG, in the IFNL4 gene encoding interferon λ4. Since the IFNL4- ΔG allele has been linked to impaired viral clearance, we hypothesized that potential exposure to sexually transmitted pathogens, as assessed by the number of lifetime sexual partners, may increase prostate cancer risk in an IFNL4- ΔG-dependent manner...
2018: Communications biology
Claudia Jaimes-Bernal, Norma Rallón, José M Benito, Mohamed Omar Mohamed-Balghata, María Amparo Gómez-Vidal, Francisco José Márquez, Beatriz Sánchez-Arcas, Monte Trujillo, José Luis Royo, Irma Saulle, Mara Biasin, Antonio Rivero-Juárez, Antonio Caruz
The IFNL4 knock-out allele (rs368234815-TT) is associated with spontaneous and IFNA-dependent cure of HCV. The role of this polymorphism in susceptibility to HIV-1 infection is controversial. This study is aimed to assess the association of this knock-out IFNL4 gene variant and sexually transmitted HIV-1 infection. 228 HIV-1 positive and 136 HIV-exposed seronegatives were investigated for their association with IFNL4 rs368234815 genotypes. The IFNL4 G functional allele is associated to increased susceptibility to HIV-1 infection through sexual route OR: 2...
October 5, 2018: Journal of Infectious Diseases
A E Grzegorzewska, M K Swiderska, W Warchol
BACKGROUND: IFNL4 polymorphisms are associated with circulating IFN-λ3, and higher plasma IFN-λ3 are associated with higher production of antibodies to HBV surface antigen (anti-HBs). The IFNL4 rs8099917 T allele and anti-HBs development in response to HBV vaccine are associated with better survival in hemodialysis (HD) patients. OBJECTIVE: To show whether plasma IFN-λ3 is also a predictor of survival in HD patients. METHOD: Plasma IFN-λ3 was measured in 135 HD patients who were followed-up for 2...
September 26, 2018: Current Molecular Medicine
Stéphanie Bibert, Agnieszka Wójtowicz, Patrick Taffé, Philip E Tarr, Enos Bernasconi, Hansjakob Furrer, Huldrych F Günthard, Matthias Hoffmann, Laurent Kaiser, Michael Osthoff, Jacques Fellay, Matthias Cavassini, Pierre-Yves Bochud
BACKGROUND: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections. OBJECTIVES: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS)...
November 28, 2018: AIDS
Enrico Galmozzi, Roberta D'Ambrosio
No abstract text is available yet for this article.
June 2018: Hepatobiliary Surgery and Nutrition
Alicja E Grzegorzewska
Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region, mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon-α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4 rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication, at least partially explains favorable HCV outcomes attributed to major homozygosity in rs12979860...
July 19, 2018: Current Medicinal Chemistry
Wei Tang, Tiffany A Wallace, Ming Yi, Cristina Magi-Galluzzi, Tiffany H Dorsey, Olusegun O Onabajo, Adeola Obajemu, Symone V Jordan, Christopher A Loffredo, Robert M Stephens, Robert H Silverman, George R Stark, Eric A Klein, Ludmila Prokunina-Olsson, Stefan Ambs
Purpose: Men of African ancestry experience an excessive prostate cancer mortality that could be related to an aggressive tumor biology. We previously described an immune-inflammation signature in prostate tumors of African-American (AA) patients. Here, we further deconstructed this signature and investigated its relationships with tumor biology, survival, and a common germline variant in the IFNλ4 ( IFNL4 ) gene. Experimental Design: We analyzed gene expression in prostate tissue datasets and performed genotype and survival analyses...
November 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Alicja E Grzegorzewska, Monika K Świderska, Leszek Niepolski, Maciej Bura, Adrianna Mostowska, Małgorzata Łagiedo-Żelazowska, Paweł P Jagodziński
Introduction Factors associated with hepatitis E virus (HEV) infection are rarely recognized in patients on renal replacement therapy (RRT), and the results of studies are inconsistent. Objectives We aimed to search for determinants of HEV seroprevalence among polymorphisms of the interferon‑λ4 gene (IFNL4) associated with seroclearance of hepatotropic viruses (IFNL4 rs12979860, rs8099917 near IFNL4), circulating interferon λ3 (IFN‑λ3), and clinical variables of patients treated with hemodialysis (HD) in a HEV‑endemic region...
June 29, 2018: Polish Archives of Internal Medicine
Alicja E Grzegorzewska, Hanna Winnicka, Wojciech Warchoł, Adrianna Mostowska, Paweł P Jagodziński
BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) contributes to maintaining immune homeostasis. Polymorphisms (SNPs) of the IDO encoding gene (IDO1) influence the IDO activity. Interferon (IFN)-λ3 induces IDO expression. We aimed to investigate whether IDO1 variants are associated with anti-HBs production in response to HBV vaccination or infection, interact with IFN-λ3 associated variants of IFNL4, and influence survival of hemodialysis (HD) patients. We also tested circulating IDO concerning IDO1 SNPs and plasma IFN-λ3 and anti-HBs levels...
July 16, 2018: Vaccine
Lisa I Backus, Troy A Shahoumian, Pamela S Belperio, Mark Winters, Ludmila Prokunina-Olsson, Thomas R O'Brien, Mark Holodniy
In direct acting antiviral (DAA)-treated HCV genotype 1, the sustained virologic response rate with the ∆G/∆G genotype of IFNL4 rs368234815 (86.8%) was significantly lower than with ∆G/TT (95.9%, P = 0.03) or TT/TT (98.6%, P = 0.01). The SVR odds ratio for ∆G/∆G compared to TT/TT was 0.10 (P = 0.03). IFNL4 genotype might predict DAA-response.
September 2018: Diagnostic Microbiology and Infectious Disease
Anand Bhushan, Sreedhar Chinnaswamy
Genetic variants at the interferon lambda (IFNL) locus have been associated with several human phenotypes in both disease and health. In chronic hepatitis C virus (HCV) infections, where the IFNL variants were first identified to be associated with response to interferon-α-ribavirin therapy, the available data clearly suggests that the causal variant could be the dinucleotide polymorphism rs368234815 that causes an open reading frame-shift in the IFNL4 gene resulting in expression of a functional IFN-λ4, a new type III IFN...
July 20, 2018: Gene
Narayan Ramamurthy, Emanuele Marchi, M Azim Ansari, Vincent Pedergnana, Angela Mclean, Emma Hudson, Rory Bowden, Chris C A Spencer, Ellie Barnes, Paul Klenerman
New directly acting antivirals (DAAs) provide very high cure rates in most patients infected by hepatitis C virus (HCV). However, some patient groups have been relatively harder to treat including those with cirrhosis or infected with HCV genotype 3. In the recent BOSON trial, genotype 3, cirrhotic patients receiving a 16 week course of sofosbuvir and ribavirin had a sustained virologic response rate (SVR) of around 50%. In cirrhotic patients, IFNL4 CC genotype was significantly associated with SVR. This genotype was also associated with a lower interferon-stimulated gene (ISG) signature in peripheral blood and in liver at baseline...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fabiana Cannella, Carolina Scagnolari, Maura Statzu, Ilaria Sciandra, Nadia Recine, Gabriella d'Ettorre, Guido Antonelli, Alessandra Pierangeli
Interferon (IFN) lambdas are important specific components of the mucosal innate immune response. The IFN lambda 4 (IFNL4) dinucleotide polymorphism (ΔG/TT) determines the IFN lambdas and related Interferon-stimulated genes activation, in HCV and other chronic infections. Our group first reported that IFN Lambda response was impaired in high-risk Human Papillomavirus (HPV) cervical infections and in precancerous lesions. Accordingly, we sought to evaluate the possible role of the IFNL4 polymorphism in determining HPV infection outcome...
April 2018: Virus Genes
Brad R Rosenberg, Catherine A Freije, Naoko Imanaka, Spencer T Chen, Jennifer L Eitson, Rachel Caron, Skyler A Uhl, Marija Zeremski, Andrew Talal, Ira M Jacobson, Charles M Rice, John W Schoggins
Polymorphisms at IFNL4 strongly influence spontaneous resolution and interferon therapeutic response in hepatitis C virus (HCV) infection. In chronic HCV, unfavorable alleles are associated with elevated interferon (IFN)-stimulated gene (ISG) expression in the liver, but extrahepatic effects are less well characterized. We used RNA sequencing (RNA-Seq) to examine whether IFNL4 genetic variation (rs368234815) modulates ISG expression in peripheral blood mononuclear cells (PBMC) during chronic HCV infection. ISG expression was elevated in unstimulated PBMC homozygous for the unfavorable ΔG IFNL4 variant; expression following IFN-α stimulation was comparable across genotypes...
January 30, 2018: Journal of Infectious Diseases
Hailiang Huang, Priya Duggal, Chloe L Thio, Rachel Latanich, James J Goedert, Alessandra Mangia, Andrea L Cox, Gregory D Kirk, Shruti Mehta, Jasneet Aneja, Laurent Alric, Sharyne M Donfield, Matthew E Cramp, Salim I Khakoo, Leslie H Tobler, Michael Busch, Graeme J Alexander, Hugo R Rosen, Brian R Edlin, Florencia P Segal, Georg M Lauer, David L Thomas, Mark J Daly, Raymond T Chung, Arthur Y Kim
Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries. We confirmed two previously reported significant associations, in the IL28B/IFNL4 and the major histocompatibility complex (MHC) regions, with spontaneous clearance in the European population...
November 20, 2017: Scientific Reports
N Ma, X Zhang, L Yang, J Zhou, W Liu, X Gao, F Yu, W Zheng, S Ding, P Gao, M Yuan, D Liu
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)...
March 2018: Journal of Viral Hepatitis
H Chen, J H Fan, W X Chen, J J Guo, Y Huang
Objective: To confirmed the polymorphisms of HLA-DQ and IFNL4 were associated with HBV infection and clearance in a Chinese population. Methods: The Sequenom MassARRAY MALDI-TOF system was used to genotype the HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917. A binary logistic regression test was conducted to estimate the relative risk of these SNPs with HBV infection and clearance. Haploview4.2 software and PHASE software (v2.0.2) were employed to analyze linkage disequilibrium (LD) and haplotype frequencies...
July 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Salvatore Petta, Luca Valenti, Antonino Tuttolomondo, Paola Dongiovanni, Rosaria Maria Pipitone, Calogero Cammà, Daniela Cabibi, Vito Di Marco, Anna Ludovica Fracanzani, Sara Badiali, Valerio Nobili, Silvia Fargion, Stefania Grimaudo, Antonio Craxì
The interferon (IFN) lambda 3/4 (IFNL3/4) locus, influencing innate immunity regulation, has been associated with the severity of hepatitis and fibrosis progression during chronic hepatitis C infection, while contrasting results were reported in nonalcoholic fatty liver disease. In this study, we examined whether rs12979860 and the linked causal rs368234815 variant encoding for the alternative IFNL4 protein variant are associated with liver fibrosis and damage in a large multicenter cohort of patients at risk of nonalcoholic steatohepatitis...
December 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Fatemeh Sakhaee, Morteza Ghazanfari, Farzam Vaziri, Fatemeh Rahimi Jamnani, Mehdi Davari, Safoora Gharibzadeh, Roohollah Fateh, Farid Abdolrahimi, Shahin Pourazar Dizaji, Abolfazl Fateh, Seyed Davar Siadat
Single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B), interferon lambda 4 (IFNL4) and the human leukocyte antigen (HLA) gene are associated with treatment responses in patients with chronic hepatitis C (CHC) virus infection treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). We compared the role of IL28B SNPs (rs12979860, rs12980275, and rs8099917), IFNL4 ss469415590 and HLA rs4273729 with treatment outcomes in patients with CHC virus. A total of 520 Iranian patients with CHC infection were enrolled...
October 2017: Infection, Genetics and Evolution
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