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Published in: Hepatology International 2/2015

01-04-2015 | Original Article

Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians

Authors: Susanne Knapp, Zainab Zakaria, Mohamed Hashem, Hassan Zaghla, Salim I. Khakoo, Imam Waked, Mark Thursz, Sayed F. Abdelwahab

Published in: Hepatology International | Issue 2/2015

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Abstract

Background/purpose

Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; also known as interleukin 28B; IL28B) gene are associated with spontaneous hepatitis C virus (HCV) clearance. Interferon lambda 4 (IFNL4).ss469415590, in linkage disequilibrium (LD) with IFNL3.rs12979860 among the Caucasian population, has recently been identified as a potential functional variant. Our objective was to assess the LD between IFNL3.rs12979860 and IFNL4.ss469415590 and to compare their effect on the outcome of HCV infection among Egyptians, mainly infected with HCV genotype 4.

Methods

One-hundred and eighty-five Egyptian HCV patients (77 spontaneous resolvers and 108 chronic subjects), and 122 healthy controls were genotyped for both IL28B.rs12979860 and IFNL4.ss469415590. Logistic regression models including factors with univariate association with the outcome of infection were calculated for each genetic marker. The LD was also calculated for the 122 healthy controls.

Results

The CC genotype of IFNL3.rs12979860 was more frequent among individuals with HCV spontaneous resolution than among those with chronic infection (57 vs. 27 %; adjusted OR 3.84; 95 % CI 2.02–7.30; p < 0.0001). Also, the TT/TT genotype of IFNL4.ss469415590 was more frequent among individuals with spontaneous resolution (49 vs. 20 %; adjusted OR 4.17; 95 % CI 2.12–8.19; p < 0.0001). Both markers were in LD (D′ = 0.96; r 2 = 0.84).

Conclusion

The IFNL3.rs12979860 and IFNL4.ss469415590 variants have comparable effects on spontaneous resolution of HCV among Egyptians, for whom both markers are closely linked.
Appendix
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Literature
1.
go back to reference Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000;284:450–456CrossRefPubMed Thomas DL, Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA 2000;284:450–456CrossRefPubMed
2.
go back to reference Thomas DL, Astemborski J, et al. The natural history of hepatitis C virus infection: host, viral and environmental factors. JAMA 2000;284:450–456CrossRefPubMed Thomas DL, Astemborski J, et al. The natural history of hepatitis C virus infection: host, viral and environmental factors. JAMA 2000;284:450–456CrossRefPubMed
3.
go back to reference Khakoo SI, Thio CL, Martin MP, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004;305:872–874CrossRefPubMed Khakoo SI, Thio CL, Martin MP, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004;305:872–874CrossRefPubMed
5.
go back to reference McFarland AP, Horner SM, Jarret A, et al. The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. Nat Immunol 2014;15:72–79CrossRefPubMedCentralPubMed McFarland AP, Horner SM, Jarret A, et al. The favorable IFNL3 genotype escapes mRNA decay mediated by AU-rich elements and hepatitis C virus-induced microRNAs. Nat Immunol 2014;15:72–79CrossRefPubMedCentralPubMed
7.
go back to reference Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010;138:1338–1345CrossRefPubMed Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic hepatitis C and treatment failure: a genome-wide association study. Gastroenterology 2010;138:1338–1345CrossRefPubMed
8.
go back to reference Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013;45:164–171CrossRefPubMedCentralPubMed Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013;45:164–171CrossRefPubMedCentralPubMed
9.
go back to reference Guerra J, Garenne M, Mohamed MK, et al. HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat 2012;19:560–567CrossRefPubMed Guerra J, Garenne M, Mohamed MK, et al. HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat 2012;19:560–567CrossRefPubMed
10.
go back to reference Simmonds P, Holmes EC, Cha TA, et al. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993;74(Pt 11):2391–2399CrossRefPubMed Simmonds P, Holmes EC, Cha TA, et al. Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993;74(Pt 11):2391–2399CrossRefPubMed
11.
go back to reference Abdel-Hamid M, El-Daly M, Molnegren V, et al. Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma. J Gen Virol 2007;88:1526–1531CrossRefPubMed Abdel-Hamid M, El-Daly M, Molnegren V, et al. Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma. J Gen Virol 2007;88:1526–1531CrossRefPubMed
12.
go back to reference El-Zayadi A, Simmonds P, Dabbous H, et al. Hepatitis C virus genotypes among HCV-chronic liver disease patients in Egypt: a leading trial. J Egypt Public Health Assoc 1994;69:327–334PubMed El-Zayadi A, Simmonds P, Dabbous H, et al. Hepatitis C virus genotypes among HCV-chronic liver disease patients in Egypt: a leading trial. J Egypt Public Health Assoc 1994;69:327–334PubMed
13.
go back to reference Abdelwahab S, Rewisha E, Hashem M, et al. Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre. Trans R Soc Trop Med Hyg 2012;106:98–103CrossRefPubMed Abdelwahab S, Rewisha E, Hashem M, et al. Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre. Trans R Soc Trop Med Hyg 2012;106:98–103CrossRefPubMed
14.
go back to reference Ray SC, Arthur RR, Carella A, et al. Genetic epidemiology of hepatitis C virus throughout Egypt. J Infect Dis 2000;182:698–707CrossRefPubMed Ray SC, Arthur RR, Carella A, et al. Genetic epidemiology of hepatitis C virus throughout Egypt. J Infect Dis 2000;182:698–707CrossRefPubMed
15.
go back to reference Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol 2005;3:S97–S101CrossRefPubMed Nguyen MH, Keeffe EB. Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6. Clin Gastroenterol Hepatol 2005;3:S97–S101CrossRefPubMed
16.
go back to reference Kurbanov F, Abdel-Hamid M, Latanich R, et al. Genetic polymorphism in IL28B is associated with spontaneous clearance of hepatitis C virus genotype 4 infection in an Egyptian cohort. J Infect Dis 2011;204:1391–1394CrossRefPubMedCentralPubMed Kurbanov F, Abdel-Hamid M, Latanich R, et al. Genetic polymorphism in IL28B is associated with spontaneous clearance of hepatitis C virus genotype 4 infection in an Egyptian cohort. J Infect Dis 2011;204:1391–1394CrossRefPubMedCentralPubMed
17.
go back to reference Derbala M, Rizk NM, Al-Kaabi S, et al. The predictive value of IL28B rs12979860, rs11881222 and rs8099917 polymorphisms and IP-10 in the therapeutic response of Egyptian genotype 4 patients. Virology 2013;444:292–300CrossRefPubMed Derbala M, Rizk NM, Al-Kaabi S, et al. The predictive value of IL28B rs12979860, rs11881222 and rs8099917 polymorphisms and IP-10 in the therapeutic response of Egyptian genotype 4 patients. Virology 2013;444:292–300CrossRefPubMed
18.
go back to reference Pasha HF, Radwan MI, Hagrass HA, et al. Cytokines genes polymorphisms in chronic hepatitis C: impact on susceptibility to infection and response to therapy. Cytokine 2013;61:478–484CrossRefPubMed Pasha HF, Radwan MI, Hagrass HA, et al. Cytokines genes polymorphisms in chronic hepatitis C: impact on susceptibility to infection and response to therapy. Cytokine 2013;61:478–484CrossRefPubMed
19.
go back to reference Pedergnana V, Abdel-Hamid M, Guergnon J, et al. Analysis of IL28B variants in an Egyptian population defines the 20 kilobases minimal region involved in spontaneous clearance of hepatitis C virus. PLoS ONE 2012;7:e38578CrossRefPubMedCentralPubMed Pedergnana V, Abdel-Hamid M, Guergnon J, et al. Analysis of IL28B variants in an Egyptian population defines the 20 kilobases minimal region involved in spontaneous clearance of hepatitis C virus. PLoS ONE 2012;7:e38578CrossRefPubMedCentralPubMed
20.
go back to reference Asselah T. A revolution in HCV treatment with direct-acting antivirals: from non-response to eradication. J Hepatol 2012;57:455–457CrossRefPubMed Asselah T. A revolution in HCV treatment with direct-acting antivirals: from non-response to eradication. J Hepatol 2012;57:455–457CrossRefPubMed
21.
go back to reference Asselah T, De Muynck S, Broet P, et al. IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C. J Hepatol 2012;56:527–532.CrossRefPubMed Asselah T, De Muynck S, Broet P, et al. IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C. J Hepatol 2012;56:527–532.CrossRefPubMed
22.
go back to reference McOmish F, Yap PL, Dow BC, et al. Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey. J Clin Microbiol 1994;32:884–892PubMedCentralPubMed McOmish F, Yap PL, Dow BC, et al. Geographical distribution of hepatitis C virus genotypes in blood donors: an international collaborative survey. J Clin Microbiol 1994;32:884–892PubMedCentralPubMed
23.
go back to reference Ohno O, Mizokami M, Wu RR, et al. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 1997;35:201–207PubMedCentralPubMed Ohno O, Mizokami M, Wu RR, et al. New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol 1997;35:201–207PubMedCentralPubMed
24.
go back to reference Knapp S, Warshow U, Ho KM, et al. A polymorphism in IL28B distinguishes exposed, uninfected individuals from spontaneous resolvers of HCV infection. Gastroenterology 2011;141:320–325CrossRefPubMedCentralPubMed Knapp S, Warshow U, Ho KM, et al. A polymorphism in IL28B distinguishes exposed, uninfected individuals from spontaneous resolvers of HCV infection. Gastroenterology 2011;141:320–325CrossRefPubMedCentralPubMed
25.
go back to reference Bibert S, Roger T, Calandra T, et al. IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 2013;210:1109–1116CrossRefPubMedCentralPubMed Bibert S, Roger T, Calandra T, et al. IL28B expression depends on a novel TT/-G polymorphism which improves HCV clearance prediction. J Exp Med 2013;210:1109–1116CrossRefPubMedCentralPubMed
26.
go back to reference Real LM, Neukam K, Herrero R, et al. IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C virus genotype 1 or 4 in Caucasians. PLoS ONE 2014;9:e95515CrossRefPubMedCentralPubMed Real LM, Neukam K, Herrero R, et al. IFNL4 ss469415590 variant shows similar performance to rs12979860 as predictor of response to treatment against Hepatitis C virus genotype 1 or 4 in Caucasians. PLoS ONE 2014;9:e95515CrossRefPubMedCentralPubMed
28.
Metadata
Title
Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians
Authors
Susanne Knapp
Zainab Zakaria
Mohamed Hashem
Hassan Zaghla
Salim I. Khakoo
Imam Waked
Mark Thursz
Sayed F. Abdelwahab
Publication date
01-04-2015
Publisher
Springer India
Published in
Hepatology International / Issue 2/2015
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-015-9619-z

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