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

Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians
Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians
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.
genotype, hcv, interferon lambda, interleukin 28, single nucleotide polymorphism, viral hepatitis
1936-0533
251-257
Knapp, S.
b7e3f8e9-0b4b-4433-8077-d6e3fbf4ccee
Zakaria, Z.
cc1605ec-3d91-4ab1-8884-5386761bcd24
Hashem, M.
88102e0b-6fb1-4489-8a40-f3e0b05f3cf7
Zaghla, H.
05eac856-c674-40d5-9641-036b2f122820
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Waked, I.
278872db-df29-4a6b-adfb-798bbe7e131d
Thursz, M.
2c345793-0ae5-4a81-b663-6c47236e2a73
Abdelwahab, S.F.
2f1b5092-b2e1-4b09-910b-e84af0aa82e0
Knapp, S.
b7e3f8e9-0b4b-4433-8077-d6e3fbf4ccee
Zakaria, Z.
cc1605ec-3d91-4ab1-8884-5386761bcd24
Hashem, M.
88102e0b-6fb1-4489-8a40-f3e0b05f3cf7
Zaghla, H.
05eac856-c674-40d5-9641-036b2f122820
Khakoo, S.I.
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Waked, I.
278872db-df29-4a6b-adfb-798bbe7e131d
Thursz, M.
2c345793-0ae5-4a81-b663-6c47236e2a73
Abdelwahab, S.F.
2f1b5092-b2e1-4b09-910b-e84af0aa82e0

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)

Record type: Article

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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More information

Accepted/In Press date: 19 February 2015
e-pub ahead of print date: 12 March 2015
Published date: April 2015
Keywords: genotype, hcv, interferon lambda, interleukin 28, single nucleotide polymorphism, viral hepatitis
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 390068
URI: http://eprints.soton.ac.uk/id/eprint/390068
ISSN: 1936-0533
PURE UUID: 3b918746-9ba3-4fb6-9f07-7cf66bb40c12
ORCID for S.I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

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Date deposited: 17 Mar 2016 16:25
Last modified: 15 Mar 2024 03:12

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Contributors

Author: S. Knapp
Author: Z. Zakaria
Author: M. Hashem
Author: H. Zaghla
Author: S.I. Khakoo ORCID iD
Author: I. Waked
Author: M. Thursz
Author: S.F. Abdelwahab

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