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- Publisher
- Wiley
- Copyright
- © 2009 Blackwell Publishing Ltd
- ISSN
- 1352-0504
- eISSN
- 1365-2893
- DOI
- 10.1111/j.1365-2893.2009.01139.x
- pmid
- 19413695
- Publisher site
- See Article on Publisher Site
Abstract
Summary. Recent reports indicated that high levels of interleukin 10 (IL‐10) contribute to the monocytes paralysis and poor clinical outcome in acute liver failure (ALF). Polymorphisms in the promoter region of IL‐10 affect IL‐10 production and confer susceptibility to inflammatory diseases. The aim of this study was to determine the possible association of the three polymorphisms (A‐1082G, T‐819C, A‐592C) in the IL‐10 gene promoter with the susceptibility to hepatitis B virus (HBV)‐related ALF in a Chinese population. The IL‐10 gene promoter polymorphisms were genotyped in 414 unrelated healthy blood donors, 367 asymptomatic HBV carriers and 345 HBV‐related ALF patients. Functional analyses were conducted to verify the biological significances of the associated genetic variations. The allele frequencies of IL‐10−592C and −819C were significantly higher in HBV‐related ALF patients than in blood donors and asymptomatic HBV carriers. Logistic regression analysis and stratification analysis with adjustment for age and sex indicated that the polymorphisms of A‐592C and T‐819C were associated with susceptibility to HBV‐related ALF (P = 6.9 × 10−7), and the ‐1082A‐819C‐592C haplotype in the IL‐10 gene promoter were associated with an increased susceptibility to ALF in HBV carriers (dominant model, P = 0.0002, odds ratio = 1.60, 95% CI 1.25–2.07). Functional analyses showed that the A‐592C polymorphism is a nuclear proteins binding site, and the disease susceptible −592C allele had a higher transcription activity compared with −592A allele. This study emphasizes the importance of IL‐10 in the pathophysiology of HBV‐related ALF on the population level.
Journal
Journal of Viral Hepatitis – Wiley
Published: Nov 1, 2009