1568. Length of TA Repeat near IL28B Could Improve The Predictive Value for HCV Spontaneous Clearance with IL28B SNPs
Session: Poster Abstract Session: Microbial and Host Genetic Factors in Disease
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • IDWeek2013ePoster-TArepeat.pdf (198.0 kB)
  • Background: Genome-Wide-Association Studies revealed that single nucleotide polymorphisms (SNPs) around interleukin (IL)-28B were associated with response to the anti-hepatitis C virus (HCV) therapy and HCV spontaneous clearance. IL28B SNPs can predict HCV clearance by anti-HCV therapy at approximately 80%. However, the remaining 20% patients show discordance between IL28B genotype and the response, suggesting that other factors might be involved in HCV clearance. We previously reported that the length of the TA dinucleotide repeat in the promoter region of IL28Bhas a wide variation and the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner. In this study, we determined the length of TA repeat to investigate the correlation to with HCV spontaneous clearance.

    Methods: Total 2041 Japanese genomic samples were enrolled (274 with HCV spontaneous clearance, 457 with chronic HCV infection and 1310 healthy donors). IL28BSNPs were genotyped using Invader assay. The length of TA repeat was determined by 3130xl sequencer and GeneMapper software.

    Results: The variation of TA repeat number ranged from 10 to 18, and the most frequent number was 12 (84.8%) in our population. A univariate analysis showed significant differences between groups with HCV spontaneous clearance and chronic infection in sex (women, 67.0% vs. 51.4%), age (68.1 ± 11.1 vs. 64.0 ± 10.8 years), IL28B (rs8099917) genotypes (TT, 92.0% vs. 67.4%), and TA repeat number (≧12/12, 99.6% vs. 95.0%) (all P≦0.01). Multiple logistic regression model showed women (OR, 2.05; 95%CI, 1.47-2.87), older age (OR, 1.03; 95%CI, 1.01-1.04), IL28B (rs8099917) genotype TT (OR, 5.40; 95%CI, 3.31-8.80), and TA repeat number ≧12/12 (OR, 10.7; 95%CI, 1.40-82.4) as independently significant factors for HCV spontaneous clearance. Analyzing these 4 factors by decision tree model, among women aged ≧68 years with IL28B (rs8099917) genotype TT, those with TA repeat genotype ≧12/12 had a high probability of spontaneous clearance.

    Conclusion: TA repeat number ≧12/12 in the promoter region of IL28B was associated to HCV spontaneous clearance. It could be the novel genetic factor to improve the predictive value for HCV clearance with IL28B SNPs.

    Satoshi Hiramine, MD.1, Masaya Sugiyama, PhD.2, Norihiro Furusyo, MD., PhD.1, Nao Nishida, PhD.2, Tsutomu Takeda, MD.2, Yoshihiko Aoki, MD.2, Masaaki Korenaga, MD., PhD.2, Kazumoto Murata, MD., PhD.2, Naohiko Masaki, MD., PhD.2, Jun Hayashi, MD., PhD.1 and Masashi Mizokami, MD., PhD.2, (1)Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan, (2)The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine (NCGM), Ichikawa, Chiba, Japan

    Disclosures:

    S. Hiramine, None

    M. Sugiyama, None

    N. Furusyo, None

    N. Nishida, None

    T. Takeda, None

    Y. Aoki, None

    M. Korenaga, None

    K. Murata, None

    N. Masaki, None

    J. Hayashi, None

    M. Mizokami, None

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