Letter: the rs12979860 and ss469415590 polymorphisms of <i>IFNL4</i> gene are in strong linkage disequilibrium in Caucasian patients with chronic hepatitis C

Keshvari, Maryam; Pouryasin, Ali; Behnava, Bita; Sharafi, Heidar; Hajarizadeh, Behzad; Alavian, Seyed Moayed

doi:10.1111/apt.12589

Cited by 11 publications

(11 citation statements)

References 4 publications

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“…The distribution of polymorphisms near IFNL3 in the current study was the same as the previous studies (28,29) in Iranian patients with HCV infection. Based on our observations, polymorphisms near IFNL3 were associated with persistence of HCV RNA in BC samples of patients with SVR.…”

Section: Discussionsupporting

confidence: 81%

“…In this study, patients with rs8099917 TG/GG were more frequently observed to have HCV RNA in their PBMC samples at the point of viremia. The mechanisms in which IFNL3 and host genetic variations causes such observation is not clear yet however discovery of IFNL4 gene near IFNL3 harboring rs12979860 and rs368234815 resulted in elucidation of different profiles of interferon stimulated genes expression, associated with treatment response to IFN-based regimens, by polymorphisms near or in IFNL3/IFNL4 genes (29,(31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

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The Role of Polymorphisms Near IFNL3 Gene as Predictors of Residual HCV RNA in Buffy Coat after Successful Antiviral Therapy

et al. 2017

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Background and Aims: The presence of the hepatitis C virus (HCV) in cells of extrahepatic organs like peripheral blood mononuclear cells (PBMCs) have important implications for transmission, disease progression, and effective treatment of HCV-infected patients. The impact of host genetics such as polymorphisms near Interferon lambda 3 (IFNL3) on clearance of HCV RNA from buffy coat (BC) following successful clearance of HCV from plasma using Pegylated-IFN (PegIFN) and Ribavirin (RBV) treatment was evaluated in our study. Methods: For detection of residual HCV RNA in BC samples, blood samples of 69 patients with sustained virologic response (SVR) after treatment with PegIFN and RBV were evaluated. Polymorphisms near IFNL3 gene including rs12979860 and rs8099917 were assessed using PCR-RFLP method. Results: The most prevalent rs12979860 and rs8099917 genotypes were CT (49.3%) and TT (62.3%), respectively. Nine (13.04%, 95%CI: 7.01% -22.96%) patients had HCV RNA in their BC samples. The favorable genotypes of the 2 polymorphisms (rs12979860 CC and rs8099917 TT) were more frequently observed in patients with undetectable HCV RNA in their BC samples than those with HCV RNA in their BC samples (rs12979860 CC, 45% vs. 22.2%, P = 0.016 and rs8099917 TT, 66.7% vs. 33.3%, P = 0.01). Conclusions:The polymorphisms of IFNL3 could play a crucial role not only in spontaneous clearance of HCV and SVR rate after PegIFN and RBV therapy, but also in the clearance of HCV from BC after PegIFN and RBV therapy.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

The Role of Polymorphisms Near IFNL3 Gene as Predictors of Residual HCV RNA in Buffy Coat after Successful Antiviral Therapy

et al. 2017

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“…In Italian patients, the IFNL4 ΔG > TT polymorphism was significantly associated with a marker for ISG activation (IP-10), but with regard to spontaneous and treatment-induced clearance, IFNL4 ΔG > TT had a predictive value similar to IFNL4 rs12979860 (Covolo et al , 2014). Two other studies also reported similar predictive values of IFNL4 ΔG > TT and IFNL4 rs12979860 polymorphisms (Keshvari et al , 2014; Stättermayer et al , 2014). Nonetheless if, as reported, one accepts the argument that IFNL4 is a functional polymorphism in the process of HCV clearance, then it would make sense to include IFNL4 ΔG > TT genotyping in clinical decisions (Keshvari et al , 2014).…”

supporting

confidence: 61%

“…Two other studies also reported similar predictive values of IFNL4 ΔG > TT and IFNL4 rs12979860 polymorphisms (Keshvari et al , 2014; Stättermayer et al , 2014). Nonetheless if, as reported, one accepts the argument that IFNL4 is a functional polymorphism in the process of HCV clearance, then it would make sense to include IFNL4 ΔG > TT genotyping in clinical decisions (Keshvari et al , 2014). …”

supporting

confidence: 61%

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

et al. 2016

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Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

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“…The perfect correlation of these two genetic variants in Caucasian patients was reported previously. [8]…”

Section: Introductionmentioning

confidence: 99%

The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C

et al. 2016

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Background:A dinucleotide variant rs368234815 in interferon lambda 4 (IFNL4) gene was recently found to be associated with the hepatitis C virus (HCV) treatment response. This study aimed to assess the impact of IFNL4 rs368234815 polymorphism on treatment response to pegylated-IFN alpha (Peg-IFN-α) and ribavirin (RBV) in hemophilic patients with chronic hepatitis C (CHC).Materials and Methods:In this retrospective study, 92 hemophilic patients with CHC who were treated with Peg-IFN-α/RBV were investigated. Single-nucleotide polymorphisms (SNPs) in IFNL genomic region including rs368234815, rs12979860, and rs8099917 were analyzed by DNA sequencing.Results:Of the 92 patients, 63 (68.5%) achieved sustained virological response (SVR). Of the 43 patients with rs368234815 TT/TT genotype, 36 (83.7%) achieved SVR, while in 49 patients with non-TT/TT genotypes, 27 (55.1%) achieved SVR. Other pretreatment parameters predicted SVR were patients’ body mass index, HCV genotype, rs12979860, and rs8099917 SNPs. In multivariate analysis, all above-mentioned parameters except rs8099917 remained as predictors of SVR. IFNL4 rs368234815 was a strong predictor of SVR; however, the prediction power of this SNP was the same as that of rs12979860 SNP in the patients of the current study.Conclusion:IFNL4 rs368234815 SNP can be considered for decision-making in the treatment of HCV-infected patients.

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Letter: the rs12979860 and ss469415590 polymorphisms of IFNL4 gene are in strong linkage disequilibrium in Caucasian patients with chronic hepatitis C

Cited by 11 publications

References 4 publications

The Role of Polymorphisms Near IFNL3 Gene as Predictors of Residual HCV RNA in Buffy Coat after Successful Antiviral Therapy

The Role of Polymorphisms Near IFNL3 Gene as Predictors of Residual HCV RNA in Buffy Coat after Successful Antiviral Therapy

Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

The interferon lambda 4 rs368234815 predicts treatment response to pegylated-interferon alpha and ribavirin in hemophilic patients with chronic hepatitis C

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