Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians
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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.
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.
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).
The IFNL3.rs12979860 and IFNL4.ss469415590 variants have comparable effects on spontaneous resolution of HCV among Egyptians, for whom both markers are closely linked.
KeywordsGenotype HCV Interferon lambda Interleukin 28 Single nucleotide polymorphism Viral hepatitis
Hepatitis C virus
National Liver Institute
Hepatitis B virus surface antigen
We thank Mrs Howayda M. Ahmed, Mrs Rehab M. El-Sayed, and Dr Mohamed A. Mahmoud (NLI Staff) for their assistance with sample collection. Mrs Enas S. Aziz (Egyblood) performed the data entry and Dr Nabiel Mikhail (South Egypt Cancer Institute) managed the data. We particularly appreciate Dr Raed S. Ibrahim (Vacsera CEO), Dr Gehan Galal (Director of Egyblood R&D Department), Dr Fatma Hamza (FP7 focal point at VACSERA), Dr Layla Bassyouni (consultant at VACSERA), and Dr Nelly Sedky and Dr Hala Hussein (former and current Egyblood CEOs, respectively) for their support throughout the conduct of the study. This study was supported by the European Union 7th Framework Program, contract no. 260844 to the HEPACUTE Consortium. The funders were not involved in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical requirements and Conflict of interest
The study protocol conformed with the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a-priori approval by the institutional review board of the Menoufiya University NLI and the Ministry of Health IRB. The consent form and procedures were approved by the NLI-IRB (NLI-IRB 00003413 FWA0000227). All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The study protocol was approved by the National Liver Institute Institutional Review Board and the Ministry of Health IRB. Informed consent was obtained from all patients for being included in the study. Susanne Knapp, Zainab Zakaria, Mohamed Hashem, Hassan Zaghla, Salim I. Khakoo, Imam Waked, Mark Thursz and Sayed F. Abdelwahab have no conflict of interest related to the work reported in this manuscript.