| BackgroundHepatitis C is a global health problem and a chronic inflammation of the liver caused by hepatitis c virus. HCV is one of the main pathogens cause liver cirrhosis and hepatocellular carcinoma. The World Health Organization estimated, there were about 3% of the world population, i.e., more than 180 million people, currently infected, with 3-4 million new cases appearing each year. HCV infection affects more than 4 million people in China, about 3.2% serum infection rates. The primary source of HCV transmission is infected blood or blood products, unsafe injection, exposure to an infected sexual partner or having multiple sexual partners, tattooing and so on. Only 20%-30% of acute HCV-infected individuals recover spontaneously, with the remaining 70%-80% going on to develop chronic infection and 30 percent of them may progress to cirrhosis and hepatocellular carcinoma. Currently, the only effective treatments of hepatitis c virus infection is based in interferon treatment, the standard of care in patients with chronic hepatitis C, a combination of PEG-IFN-αwith ribavirin, does not produce SVR in all patients treated. In antiviral treatment process, several viral factors, such as genotype 1, high baseline viral load, viral kinetics during treatment, and amino acid pattern in the interferon sensitivity-determining region, these factors are significantly associated with the treatment outcome. However, only 42-52% of patients with hepatitis C genotype 1 on 48-week-long treatment can achieve sustained virologic response, and 5% of patients with genotype 2 or 3 have a null response to PEG-IFN-α/RBV, and 10-14% of patients require premature withdrawal from interferon-based therapy due to the side effects.In recent years, in Africa, Europe and East Asia cohorts, using Genome-wide Association Study identified Single Nucleotide Polymorphism in the IL-28B (encode IFNλ3) region as associated with spontaneous clearance of HCV and an effect on treatment response of interferon. Genetic variance could influence the spontaneous clearance of HCV and response to interferon of patients with hepatitis c. A single nucleotide polymorphism (rs8099917) located 8kb upstream of IL28B gene which located on chromosome 19 and encode IFN-λ3. Suppiah et al. and Rauch et al. demonstrated IL-28B polymorphisms in European cohorts, which were associated with an effect on treatment response and on treatment failure, respectively. Tanaka et al. identified IL-28B SNP rs8099917 to be associated with SVR in Japanese patients, which is a more profound effect than in European cohorts. They also found that SNP rs12980275 was associated with treatment response. The T/T genotype of rs8099917 can achieve SVR more possibly than G/G genotype. The A/A genotype of rs8099917 can also achieve SVR more possibly than G/G genotype.ObjectiveAt present, the relationship of IL28 alleles and interferon response is rare reported in our country. Therefore, we can retrospective study the condition of treatment response of interferon and IL28B gene polymorphism of chronic hepatitis c in our hospital, and compare with IL28B gene variants frequency of sustained virological response group and null virological response. To early predict curative effect of interferon provide theoretical basis. Methods1. Cases collected:Selected cases were all chronic hepatitis c patients, the diagnostic standard meets the criteria drawn up by Hepatology branch of Chinese medical association on March 2004, genotype is all HCV 1 type, and they are all accept antiretroviral treatment with a combination of interferon IFN and ribavirin (RBV) for one year, six months latter test HCV-RNA.2. Experimental methods:Collecting the peripheral blood treated by EDTA of these patients, using the molecular biology methods extract human genomic DNA, after PCR directly sequencing. The test was done by sequencing for SNPs genotyping of rs8099917 and rs12980275 of sustained virological response and null virological response patients. The allele frequency between the patients with sustained virological response and null virological response were compared to assess the effect of SNP.3. Statistical analysis:SPSS 17.0 statistics software was used to analyze data. We analyze gene phenotype and allele frequency of the IL28B gene polymorphism rs12980275 and rs8099917 for patients of chronic hepatitis c of interferon antiviral treatment response and not response, and allele single factor analysis and correlation analysis are used Pearson X 2 and relevance test. Compare the frequency difference of response group and not response groups, use odds ratio and 95% confidential interval signify relative risk degrees, R signify relevance. P value bilateral,α= 0.05, regard P< 0.05 as statistical significance. R> 0 for positive correlation, R< 0 for negatively correlated.Results1. Genotype Frequency:In 63 SVR patients, rs12980275 genotypes distribution (A/A n=55,87%; A/G n=8,13%), in 34 NVR patients, rs12980275 genotypes distribution (A/A n=23,68%; A/G n=11,32%). There was significant difference between the two groups (OR=3.288,95%CI=[1.171-9.234], Pearson's x 2=5.416, P=0.020<0.05), and positive correlation between the two groups (Pearson's R=0.236>0). In 63 SVR patients, rs8099917 genotypes distribution (T/T n=55,87%; T/G n=8, 13%), in 34 NVR patients, rs8099917 genotypes distribution (T/T n=24,71%; T/G n=10,29%). There was significant difference between the two groups (OR=2.865, 95%CI=[1.006-8.154], Pearson's x 2=4.081, P=0.043<0.05), and positive correlation between the two groups (Pearson's R=0.205>0).Two genotypes (TT and TG of rs8099917, AA and AG of rs12980275) were identified in the study. No GG genotype was founded.2. The frequency of A allele of rs12980275 was 93.7% verse 83.8% and G allele frequency is 6.3% verse 16.2% in SVR patients and NVR patients, respectively. There was significant difference between the two groups (OR=2.846, 95%CI= [1.086-7.464], Pearson's x2=4.828, P=0.028<0.05), and positive correlation between the two groups (Pearson's R=0.158>0).The frequency of T allele of rs8099917 was 93.7% verse 85.3% and G allele frequency is 6.3% verse 14.7% in SVR patients and NVR patients, respectively. There was no significant difference between the two groups (OR=2.543, 95%CI=[0.953-6.785], Pearson's X2=3.664, P=0.056>0.05), and positive correlation between the two groups (Pearson's R=0.137>0).Conclusion1. There was significant difference between the A allele of rs12980275 (93.7% to 83.8%) and G allele (6.3% to 16.2%) in SVR patients and NVR patients.There was no significant difference between the T allele of rs8099917 (93.7% to 85.3%) and G allele (6.3% to 14.7%) in SVR patients and NVR patients.2. Genotype of rs12980275 mainly are AA, AG, GG, rs12980275 mainly are TT, TG, GG, but in our studies rs12980275 only detect AA, AG, rs8099917 only detect TT and TG, there were not found GG type in both rs8099917 and rs 12980275, and the proportion of GG type of rs8099917 and rs12980275 very low.3. Polymorphism of SNPs rs8099917 and rs12980275 can effectively predict interferon antiviral treatment response effect. |
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