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

Publication ,  Journal Article
Cyr, DD; Lucas, JE; Thompson, JW; Patel, K; Clark, PJ; Thompson, A; Tillmann, HL; McHutchison, JG; Moseley, MA; McCarthy, JJ
Published in: PLoS One
2011

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.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

7

Start / End Page

e21854

Location

United States

Related Subject Headings

  • Transcortin
  • Proteomics
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Interleukins
  • Interferons
  • Humans
  • Hepatitis C, Chronic
 

Citation

APA
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ICMJE
MLA
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Cyr, D. D., Lucas, J. E., Thompson, J. W., Patel, K., Clark, P. J., Thompson, A., … McCarthy, J. J. (2011). Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C. PLoS One, 6(7), e21854. https://doi.org/10.1371/journal.pone.0021854
Cyr, Derek D., Joseph E. Lucas, J Will Thompson, Keyur Patel, Paul J. Clark, Alexander Thompson, Hans L. Tillmann, John G. McHutchison, M Arthur Moseley, and Jeanette J. McCarthy. “Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C.PLoS One 6, no. 7 (2011): e21854. https://doi.org/10.1371/journal.pone.0021854.
Cyr DD, Lucas JE, Thompson JW, Patel K, Clark PJ, Thompson A, et al. Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C. PLoS One. 2011;6(7):e21854.
Cyr, Derek D., et al. “Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C.PLoS One, vol. 6, no. 7, 2011, p. e21854. Pubmed, doi:10.1371/journal.pone.0021854.
Cyr DD, Lucas JE, Thompson JW, Patel K, Clark PJ, Thompson A, Tillmann HL, McHutchison JG, Moseley MA, McCarthy JJ. Characterization of serum proteins associated with IL28B genotype among patients with chronic hepatitis C. PLoS One. 2011;6(7):e21854.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

7

Start / End Page

e21854

Location

United States

Related Subject Headings

  • Transcortin
  • Proteomics
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Mass Spectrometry
  • Male
  • Interleukins
  • Interferons
  • Humans
  • Hepatitis C, Chronic