IL28B genetic variation is associated with spontaneous clearance of hepatitis C virus, treatment response, serum IL-28B levels in Chinese population.
BACKGROUND
The interleukin-28B gene (IL28B) locus has been associated with host resistance to hepatitis C virus (HCV) infection and response to PEG-IFN/RBV treatment in western populations. This study was to determine whether this gene variant is also associated with spontaneous clearance of HCV infection, treatment response and IL-28B protein production in Chinese patients.


METHODS
We genotyped IL28B genetic variations (rs12980275, rs8103142, rs8099917 and rs12979860) by pyrosequencing DNA samples from cohorts consisting of 529 subjects with persistent HCV infection, 196 subjects who cleared the infection, 171 healthy individuals and 235 chronic HCV patients underwent IFN/RBV treatment. The expression of IL-28B were measured by ELISA and RT-PCR.


RESULTS
We found that the four IL28B variants were in complete linkage disequilibrium (r2 = 0.97-0.98). The rs12979860 CC genotype was strongly associated with spontaneously HCV clearance and successful IFN/RBV treatment compared to the CT/TT. IL-28B levels in persistent HCV patients were significantly lower than subjects who spontaneously resolved HCV and healthy controls and were also associated with high levels of ALT (alanine aminotransferase) and AST (aspartate aminotransferase). IL-28B levels were also significantly lower in individuals carrying T alleles than CC homozygous.


CONCLUSIONS
Thus, the rs12979860-CC variant upstream of IL28B gene is associated with spontaneous clearance of HCV, susceptible to IFN/RBV treatment and increased IL-28B levels in this Chinese population.
Department of Hepatology, First Hospital of Jilin University, Changchun, China.
Xiaodong
X
Shi
Yu
Y
Pan
Moli
M
Wang
Dongsheng
D
Wang
Wanyu
W
Li
Tao
T
Jiang
Peng
P
Zhang
Xiumei
X
Chi
Yanfang
Y
Jiang
Yanhang
Y
Gao
Jin
J
Zhong
Bing
B
Sun
Damo
D
Xu
Jing
J
Jiang
Junqi
J
Niu
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D004797:Enzyme-Linked Immunosorbent Assay; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000097:blood* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000095022:Interferon Lambda
D007372:Interferons; D007378:Interleukins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda