Regulatory polymorphisms in the IL-10 gene promoter and HBV-related acute liver failure in the Chinese population.
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 x 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.
Department of Infectious Diseases, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Z
Z
Yan
W
W
Tan
W
W
Zhao
Y
Y
Dan
X
X
Wang
Q
Q
Mao
Y
Y
Wang
G
G
Deng
D000328:Adult; D044466:Asian People / Q000235:genetics*; D002353:Carrier State / Q000503:physiopathology / Q000821:virology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006509:Hepatitis B / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D006515:Hepatitis B virus / Q000472:pathogenicity; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D017114:Liver Failure, Acute / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
D016753:Interleukin-10