The impact of genetic variation in IL28B, IFNL4 and HLA genes on treatment responses against chronic hepatitis C virus infection

Sakhaee, Fatemeh; Ghazanfari, Mehdi; Vaziri, Farzam; Jamnani, Fatemeh Rahimi; Davari, Mehdi D.; Gharibzadeh, Safoora; Fateh, Roohollah; Abdolrahimi, Farid; Dizaji, Shahin Pourazar; Fateh, Abolfazl; Siadat, Seyed Davar

doi:10.1016/j.meegid.2017.07.023

Cited by 21 publications

(19 citation statements)

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“…Numerous reports indicated that the unfavorable IFNL3 and IFNL4 genotypes are associated with reduced response to pegIFN‐α/RBV therapy and augmented the frequency of HCV infection in PBMCs . The impact of IFNL3 rs12979860 genotypes on OCI is controversial.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…All selected patients were genotyped for the SNPs of the IFNL3 gene (rs12979860, rs8099917, and rs12980275) and IFNL4 ss469415590 polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan® Real-Time SNP Assays, respectively, as previously described. 12,13 Hepatitis C virus detection and genotyping Plus-and minus-strand HCV-RNA in PBMC samples were detected by nested RT-PCR using primers of the HCV 5 0untranslated region named SF1/SF2 and SR1/SR2 for plusand minus-strand HCV-RNA, respectively, as previously described. 14 Briefly, this method was carried out in a 25-μL final volume containing 1× reaction buffer (Sinaclon, Tehran, Iran), 0.4 mM of each nucleotide, 2 U/μL Taq DNA polymerase, 3 mM MgCl 2 , and 10 pmol of each primer (SF1 or SR1).…”

Section: Ifnl3 and Ifnl4 Snps Genotypingmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) in IFNL gene loci, mainly rs12979860 of the IFNL3 gene, are correlated with spontaneous HCV clearance and sustained viral response (SVR) to treatment with pegylated interferon‐α and ribavirin (pegIFN‐α/RBV). Also, there is strong linkage disequilibrium (LD) of IFNL3 rs12979860 with IFNL4 ss469415590, which is correlated with HCV therapeutic eradication …”

Section: Introductionmentioning

confidence: 99%

“…Also, there is strong linkage disequilibrium (LD) of IFNL3 rs12979860 with IFNL4 ss469415590, which is correlated with HCV therapeutic eradication. 11,12 To date, no comprehensive study has determined the association between host genetic factors and clinical parameters with OCI in patients on CHD. Therefore, the current study aimed at evaluating the frequency of OCI in patients on CHD and assessing the correlation between OCI incidence with clinical parameters and IFNL3 SNPs (rs12979860, rs8099917, and rs12980275) and IFNL4 ss469415590.…”

Section: Introductionmentioning

confidence: 99%

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Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Ayadi

Nafari

Sakhaee

et al. 2019

Hepatology Research

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Aim The presence of occult hepatitis C virus (HCV) infection (OCI) is still controversial, however, this infection cannot be ignored. Therefore, the current study aimed at assessing the OCI frequency in patients on chronic hemodialysis (CHD) and also evaluating the association between OCI incidence with clinical parameters and interferon lambda 3/4 (IFNL3/4) gene polymorphisms. Methods A total of 515 patients on CHD and HCV negative markers were selected. Plus‐ and minus‐stranded HCV‐RNA was tested in peripheral blood mononuclear cell samples by reverse transcription–polymerase chain reaction and then genotyped using the restriction fragment length polymorphism method. Results The frequency of OCI was 11.3% in patients on CHD. Among 58 patients with OCI, 25.8%, 62.1%, and 12.1% were infected with HCV‐1a, HCV‐1b, and HCV‐3a, respectively. The mean alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were 31.9 ± 24.8, 32.3 ± 19.1, and 171.6 ± 88.9, respectively. None of the patients with OCI had a history of liver disease. Multivariate logistic regression analysis indicated that cholesterol, triglyceride, low‐density lipoprotein, 25‐hydroxyvitamin D, platelets, duration of hemodialysis, HCV subtypes, IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ΔG/ΔG genotypes were associated with OCI. Conclusion There was a moderate prevalence of OCI in Iranian patients on CHD. The current study findings indicated that this infection was associated with clinical parameters and unfavorable genotypes of IFNL3 single nucleotide polymorphisms and IFNL4 ss469415590. Further studies are required to determine the correlation between OCI incidence with clinical parameters and host genetic factors.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ifnl3 and Ifnl4 Snps Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Ayadi

Nafari

Sakhaee

et al. 2019

Hepatology Research

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Occult hepatitis C virus infection in patients with beta‐thalassemia major: Is it a neglected and unexplained phenomenon?

Ayadi

Nafari

Irani

et al. 2019

J of Cellular Biochemistry

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Occult hepatitis C virus (HCV) infection (OCI) is described as the presence of viral genome in both hepatocytes and peripheral blood mononuclear cells (PBMCs) despite constant negative results on serum HCV RNA tests. Betathalassemia major (BTM) describes a group of inherited blood diseases. Patients with BTM require repeated blood transfusions, increasing the risk of exposure to infectious agents. We aimed to assess the prevalence of OCI in Iranian BTM patients and to identify the role of host factors in OCI positivity. A total of 181 BTM patients with HCV negative markers were selected. HCV RNA was tested in PBMCs using nested polymerase chain reaction assay. The positive samples were then genotyped via restriction fragment-length polymorphism (RFLP) and 5′-untranslated region sequencing. Six (3.3%) out of 181 BTM patients had viral HCV genomes in PBMC samples. Three (50.0%), two (33.3%), and one (16.7%) out of these six patients were infected with HCV-1b, HCV-1a, and HCV-3a, respectively. OCI positivity was significantly associated with the serum level of uric acid (P = 0.045) and ABO blood group (P = 0.032). Also, OCI patients had unfavorable IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 ss469415590 ΔG/ΔG genotypes. In conclusion, we indicated the low frequency of OCI in BTM patients. Nevertheless, more attention is warranted considering the importance of this infection. Also, further studies are necessary to determine the actual prevalence of OCI among BTM patients in Iran.

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Investigating the role of killer cell immunoglobulin‐like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection

Li,

Zeng,

Huang

et al. 2024

Journal of Medical Virology

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The genetic diversity of killer cell immunoglobulin‐like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA‐A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case‐control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA‐A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA‐A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

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The impact of genetic variation in IL28B, IFNL4 and HLA genes on treatment responses against chronic hepatitis C virus infection

Cited by 21 publications

References 23 publications

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Host genetic factors and clinical parameters influencing the occult hepatitis C virus infection in patients on chronic hemodialysis: Is it still a controversial infection?

Occult hepatitis C virus infection in patients with beta‐thalassemia major: Is it a neglected and unexplained phenomenon?

Investigating the role of killer cell immunoglobulin‐like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection

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