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

Knapp, S., Zakaria, Z., Hashem, M., Zaghla, H., Khakoo, S.I., Waked, I., Thursz, M. and Abdelwahab, S.F. (2015) Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians. Hepatology International, 9 (2), 251-257. (doi:10.1007/s12072-015-9619-z). (PMID:25788203)

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.

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Contributors

Author: S.I. Khakoo

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