Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C

Cyr, Derek D., Lucas, Joseph E., Thompson, J. Will, Patel, Keyur, Clark, Paul J., Thompson, Alexander, Tillmann, Hans L., McHutchison, John G., Moseley, M. Arthur and McCarthy, Jeanette J. (2011) Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C. PLoS One, 6 7: 1-6. doi:10.1371/journal.pone.0021854


Author Cyr, Derek D.
Lucas, Joseph E.
Thompson, J. Will
Patel, Keyur
Clark, Paul J.
Thompson, Alexander
Tillmann, Hans L.
McHutchison, John G.
Moseley, M. Arthur
McCarthy, Jeanette J.
Title Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C
Formatted title
Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2011-07-05
Sub-type Article (original research)
DOI 10.1371/journal.pone.0021854
Open Access Status DOI
Volume 6
Issue 7
Start page 1
End page 6
Total pages 6
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Introduction: Polymorphisms near the IL28B gene (e.g. rs12979860) encoding interferon λ3 have recently been associated with both spontaneous clearance and treatment response to pegIFN/RBV in chronic hepatitis C (CHC) patients. The molecular consequences of this genetic variation are unknown. To gain further insight into IL28B function we assessed the association of rs12979860 with expression of protein quantitative traits (pQTL analysis) generated using open-platform proteomics in serum from patients.
Methods: 41 patients with genotype 1 chronic hepatitis C infection from the Duke Liver Clinic were genotyped for rs12979860. Proteomic profiles were generated by LC-MS/MS analysis following immunodepletion of serum with MARS14 columns and trypsin-digestion. Next, a latent factor model was used to classify peptides into metaproteins based on co-expression and using only those peptides with protein identifications. Metaproteins were then analyzed for association with IL28B genotype using one-way analysis of variance.
Results:
There were a total of 4,186 peptides in the data set with positive identifications. These were matched with 253 proteins of which 110 had two or more associated, identified peptides. The IL28B treatment response genotype (rs12979860_CC) was significantly associated with lower serum levels of corticosteroid binding globulin (CBG; p = 9.2×10-6), a major transport protein for glucocorticoids and progestins. Moreover, the CBG metaprotein was associated with treatment response (p = 0.0148), but this association was attenuated when both IL28B genotype and CBG were included in the model, suggesting that the CBG association may be independent of treatment response.
Conclusions: In this cohort of chronic hepatitis C patients, IL28B polymorphism was associated with serum levels of corticosteroid binding globulin, a major transporter of cortisol, however, CBG does not appear to mediate the association of IL28B with treatment response. Further investigation of this pathway is warranted to determine if it plays a role in other comorbidities of HCV-infection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 16 Sep 2014, 12:49:41 EST by Ms Kate Rowe on behalf of School of Medicine