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HBV : PE-033 ; Association between IL28B polymorphism and spontaneous clearance of hepatitis B virus
( Seung Up Kim ),( Hye Young Chang ),( Jun Yong Park ),( Do Young Kim ),( Kwang Hyub Han ),( Chae Yoon Chon ),( Sang Hoon Ahn ) 대한간학회 2012 춘·추계 학술대회 (KASL) Vol.2012 No.1
Background: The association between IL28B polymorphism and spontaneous clearance of HBV infection has been available in only one study, reported as a brief article. Thus, we analyzed this association in a large cohort with chronic hepatitis B (CHB) and investigated whether there is any novel polymorphism in the DNA sequence of IL28B genome. Methods: Between January 2007 and June 2010, a total of 208 patients who have suffered from CHB infection and newly diagnosed CHB-related hepatocellular carcinoma (HCC) were prospectively recruited and defined as CC group [HBsAg (+) for over 6 months, anti-HBc (+), and anti-HBs (-)]. During the study period, a total of 351 living liver or kidney donors were also prospectively recruited and stratified into UE group [n=106; HBsAg (-), anti-HBc (-), and anti-HBs (-)] or SC group [n=245; HBsAg (-), anti-HBc (+), and anti-HBs (+)] according to their HBV serological markers. For the detection of the three SNPs (rs12979860, rs12980275, and rs8099917) near the IL28B gene, primer extension reactions were performed using SNaPshot ddNTP Primer Extension Kit (Applied Biosystem, Foster City, CA). Nine primer sets were used to amplify IL28B coding region. Results: All patients had HBV genotype C. The non-genetic factors including age and male gender was similar among the groups (all p>0.05). Regardless of groups, rs12979860 CC was most frequently identified in more than 85% of patients in each group (85.0% in UE, 85.9% in SC, and 93.5% in CC group, respectively) whereas rs12979860 TT were not identified in any group (0% in all groups). Similarly, rs12980275 AA and rs8099917 TT was most frequently identified (≥85%), regardless of subject groups, whereas rs12980275 GG was identified in only one subject in SC group and rs8099917 GG was not identified. Using randomly selected 50 samples from each group for full sequencing of IL28B coding region, we found 19 novel SNPs. Of these, 6 SNPs (SNP2, 5, 7, 8, 17, and 19) were significantly different among UE, SC, and CC groups (all p<0.05). Regardless of groups, SNP2 TT (84.0~86.3%), SNP5 CC (92.0~97.1%), SNP7 GG (84.0~92.7%), SNP8 GG (84.0~ 94.7%), SNP17 AA (94.0~98.8%), and SNP19 GG (82.0~ 93.0%) was most frequently identified. Conclusions: Our data suggest that the SNP upstream of IL28B has no effect on HBV recovery. Additional studies are needed to understand the mechanisms underlying the beneficial effect of this SNP in HCV infection but not in HBV infection and investigate the clinical implication of the newly identified 6 SNPs in IL28B genome.