Skip to main content

A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection.

Publication ,  Journal Article
Thomas, R; Thio, CL; Apps, R; Qi, Y; Gao, X; Marti, D; Stein, JL; Soderberg, KA; Moody, MA; Goedert, JJ; Kirk, GD; Hoots, WK; Wolinsky, S ...
Published in: J Virol
June 2012

Variants near the HLA-DP gene show the strongest genome-wide association with chronic hepatitis B virus (HBV) infection and HBV recovery/persistence in Asians. To test the effect of the HLA-DP region on outcomes to HBV infection, we sequenced the polymorphic HLA-DPB1 and DPA1 coding exons and the corresponding 3' untranslated regions (3'UTRs) in 662 individuals of European-American and African-American ancestry. The genome-wide association study (GWAS) variant (rs9277535; 550A/G) in the 3'UTR of the HLA-DPB1 gene that associated most significantly with chronic hepatitis B and outcomes to HBV infection in Asians had a marginal effect on HBV recovery in our European- and African-American samples (odds ratio [OR] = 0.39, P = 0.01, combined ethnic groups). However, we identified a novel variant in the HLA-DPB1 3'UTR region, 496A/G (rs9277534), which associated very significantly with HBV recovery in both European and African-American populations (OR = 0.37, P = 0.0001, combined ethnic groups). The 496A/G variant distinguishes the most protective HLA-DPB1 allele (DPB1*04:01) from the most susceptible (DPB1*01:01), whereas 550A/G does not. 496A/G has a stronger effect than any individual HLA-DPB1 or DPA1 allele and any other HLA alleles that showed an association with HBV recovery in our European-American cohort. The 496GG genotype, which confers recessive susceptibility to HBV persistence, also associates in a recessive manner with significantly higher levels of HLA-DP surface protein and transcript level expression in healthy donors, suggesting that differences in expression of HLA-DP may increase the risk of persistent HBV infection.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

June 2012

Volume

86

Issue

12

Start / End Page

6979 / 6985

Location

United States

Related Subject Headings

  • Virology
  • Racial Groups
  • Humans
  • Hepatitis B virus
  • Hepatitis B
  • HLA-DP beta-Chains
  • HLA-DP alpha-Chains
  • Genome-Wide Association Study
  • Genetic Variation
  • Cohort Studies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Thomas, R., Thio, C. L., Apps, R., Qi, Y., Gao, X., Marti, D., … Carrington, M. (2012). A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection. J Virol, 86(12), 6979–6985. https://doi.org/10.1128/JVI.00406-12
Thomas, Rasmi, Chloe L. Thio, Richard Apps, Ying Qi, Xiaojiang Gao, Darlene Marti, Judy L. Stein, et al. “A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection.J Virol 86, no. 12 (June 2012): 6979–85. https://doi.org/10.1128/JVI.00406-12.
Thomas R, Thio CL, Apps R, Qi Y, Gao X, Marti D, et al. A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection. J Virol. 2012 Jun;86(12):6979–85.
Thomas, Rasmi, et al. “A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection.J Virol, vol. 86, no. 12, June 2012, pp. 6979–85. Pubmed, doi:10.1128/JVI.00406-12.
Thomas R, Thio CL, Apps R, Qi Y, Gao X, Marti D, Stein JL, Soderberg KA, Moody MA, Goedert JJ, Kirk GD, Hoots WK, Wolinsky S, Carrington M. A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection. J Virol. 2012 Jun;86(12):6979–6985.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

June 2012

Volume

86

Issue

12

Start / End Page

6979 / 6985

Location

United States

Related Subject Headings

  • Virology
  • Racial Groups
  • Humans
  • Hepatitis B virus
  • Hepatitis B
  • HLA-DP beta-Chains
  • HLA-DP alpha-Chains
  • Genome-Wide Association Study
  • Genetic Variation
  • Cohort Studies