The Association Of IL28B Genetic Variation And Hepatitis C

Background and objectives:Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide. The disease affects 37-40 million people in china with 3-4 million new cases appearing each year. 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. 80 percent of patients with hepatitis C develop chronic hepatitis and 30 percent of them may progress to cirrhosis and hepatocellular carcinoma. The recommended treatment for patients with chronic hepatitis C is 48-week pegylated interferon-a plus ribavirin (RBV).However, only 42-52% of patients with hepatitis C genotype 1 can achieve sustained virologic response, and 10-14% of patients require premature withdrawal from interferon-based therapy due to the side effects. In a recent genome-wide association study, a single nucleotide polymorphism(rs12979860) 3 kilobases upstream of the IL28B gene, which encodes the typeⅢinterferon IFN-λ3, was strongly associated with natural clearance of HCV and SVR. The C/C genotype can achieve clearance of HCV and SVR more possibly than T/T genotype.The C/C genotype was associated with a 2 or greater rate of SVR compared with the T/T genotype in European people. The same results also appeared in Africa people and Hispanic people. Compared to other factors like baseline viral load, fibrosis and ethnicity, IL28B genetic variation not only strongly influences SVR, but also appear to explain much of the differences between different population groups. The identification of the SNP shows significant association for the patients with hepatitis C prior to treatment. Owing to the geographic difference, economic status, population, epidemiology, and host or viral factors, study of IL28B genetic variation in Chinese population shows significantly association. The main objective of the study, therefore, is to analyze the IL28B genetic variation in Chinese population and its relevance with SNP and hepatitis C.Method:411 hepatitis C patients, 255 male and 186 female and 100 healthy controls were enrolled in the study. The anti-HCV was tested through the domestic reagent and imported reagent. The average age of individuals is 49.11 with a 1.21 to 1 male to female ratio. The anti-HCV positive patients were further tested for HCV-RNA. Patients with undetectable serum viral RNA and detectable viral RNA were grouped as spontaneously cleard HCV and chronically infected groups, respectively. The diagnostic standard meets the criteria drawn up by Hepatology branch of Chinese medical association on March 2004. The test was done by Pyrosequencing for SNP Genotyping of rs12979860 which resides 3kilobases upstream of IL28B gene. The allele frequency between the patients with hepatitis C and healthy controls were compared to assess the effect of SNP, baseline virus load, liver function, and genotype on the treatment and prognosis of HCV. SAS and SPSS statistics software were used to testχ2 and OR values.Result:1. Two genotypes, TC and CC, were identified in the study. No TT genotype was founded.2. The frequency of C allele was 94% verse 96.7% and T allele frequency is 6% verse 3.3% in hepatitis C patients and healthy controls respectively. There was no significant relationship between the two groups (χ2= 3.23, Pearson's p value is 0.07>0.05).3. There was no significant difference between the CC genotype (88% to 93.4%) and TC genotype (12% to 6.6%) in hepatitis C patients and healthy controls.4. From the total of 394 patients who had tested for HCV-RNA, 60 (15%) and 34 cases(9%) were positive with the Baseline viral load less than 15IU/ml ;12 (3%) were 15-100IU/ml.16 (4%) were 102 to 103IU/ml. 28 (7%) were 103 to 104IU/ml. 32 (8%) were 104 to 105IU/ml. 75 cases(19%) were 105 to 106IU/ml.123 cases(31%) were 106 to 107IU/ml and 15 cases in the value more than 107IU/ml.5. 152 cases had abnormal ALT (>50U/L) and 133 cases had the abnormal AST (>40U/L). The average values of ALT and AST were 58.95U/L and 49.07U/L, respectively.6. There are no significant correlation between baseline viral load more than 15IU/ml and ALT value (r = -0.045, P =0.45). Similar findings were obtained from the linear regression equation y=-1.9627x+77.579, R2=0.002.7. 369 cases were genotype CC and 25 cases were genotype CT. Combined with baseline viral load, there was a statistically significant difference the genotype CC and TT groups (Z =-2.31, P = 0.02).8. There were 57 cases of genotype CC and 3 cases of genotype CT among the patients with undetectable serum HCV-RNA. There was no significant relationship between the two genotypes (P =0.64 and OR=1.34, 95%CI 0.39~4.61).9. 143 cases of genotype CC and 9 cases of genotype CT had abnormal ALT value (>50U/L), but the difference was not statistically significant between the two groups (P = 0.667).10. 68 cases with Baseline viral load greater than 106 were tested for HCV-RNA genotypes. 38(55.9%) were genotype 1b, 27(39.7%) were genotype 2a and 3(4.4%) were unclassified Genotype.11. From the 38 genotype 1b cases, 37 were CC and 1 case was CT likewise from the 27 genotype 2a, 25 were CC and 2 cases were TT. (P = 0.565).Conclusion:1. The C allele frequency (rs12979860) was similar between patients with hepatitis C and healthy controls. The C allele frequency of Chinese population is close to Japanese population but different with European-Americans.2. There are no difference of genotype (rs12979860) between hepatitis C patients and healthy controls. The main genotype was CC (>88%). Although no homozygous genotype TT was found, all cases were according to Hardy-Weinberg Equilibrium.3. 15% of hepatitis C patients in north-china spontaneously clear HCV. 50% of the patients whose baseline viral load was greater than 105 IU/ml were develop chronic HCV infection4. There are no association between ALT value and Baseline viral load. The ALT value doesn't vary with change in Baseline viral load.5. Either Baseline viral load or SNP could be used to assess the treatment prognosis of hepatitis C patients independently. The baseline viral load concentration in genotype CC was greater than TT.6. There was no significance difference between the genotype CC and TC among individuals who spontaneously clear HCV, this could be because of the difference in the number of patients between the two groups.7. There are no significant difference between ALT value and genotype.8. The main HCV genotypes were 1b and 2a among the patients in north-china.9. Although there are no significant difference between HCV genotype and SNP, the combination of the two factors can be used to determine the patients before treatment.