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J Gastroenterol. 2012 May;47(5):596-605. doi: 10.1007/s00535-012-0531-1. Epub 2012 Mar 23.

Association of two polymorphisms of the IL28B gene with viral factors and treatment response in 1,518 patients infected with hepatitis C virus.

Author information

  • 1Research Institute for Hepatology, Toranomon Hospital, 1-3-1, Kajigaya, Takatsu-ku, Kawasaki, 213-8587, Japan. vj7m-kbys@asahi-net.or.jp

Abstract

BACKGROUND:

Two nucleotide polymorphisms of the interleukin-28B (IL28B) gene, at rs8099917 and rs12979860, influence the response to interferon (IFN)-based therapies in patients infected with hepatitis C virus (HCV) of genotype 1. We aimed to investigate whether these polymorphisms showed complete linkage in Japanese patients.

METHODS:

A total of 1,518 Japanese patients infected with HCV were genotyped for the two IL28B loci, and the two sets of genotypes were compared.

RESULTS:

TT at rs8099917 and CC at rs12979860 were detected in 77.7 and 76.8%, respectively, of the 1,518 patients and TG/GG and CT/TT were detected in 22.3 and 23.2%. These two sets of IL28B genotype stood in strong linkage disequilibrium (r (2) = 0.98). Discordance between the two IL28B polymorphisms occurred in 16 (1.1%) patients, and 13 (0.9%) of them possessed IFN-sensitive TT at rs8099917 and IFN-resistant CT at rs12979860. Three of these 13 patients had HCV of genotype 1b and had received pegylated-interferon and ribavirin, and none of them gained a sustained virological response. At rs8099917, IFN-resistant TG/GG were more frequent in patients infected with HCV of genotype 1 than in those infected with HCV of genotype 2 [258/1,046 (24.7%) vs. 75/441 (17.0%), p = 0.001]. The response to pegylated-interferon/ribavirin in 279 patients who were infected with HCV-1 and the response to IFN monotherapy in 361 patients who were infected with HCV-1 , was higher in those with TT than in those with TG/GG at rs8099917, as well as being higher in those with CC than in those with CT/TT at rs12979860 (p < 0.001).

CONCLUSIONS:

Linkage disequilibrium between two IL28B polymorphisms at rs8099917 and rs12979860 is strong in Japanese HCV patients, but there are some discrepancies between the two sets of genotypes.

PMID:
22438096
[PubMed - indexed for MEDLINE]
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