Association Between Interleukin-28B Polymorphisms And Susceptibility To Hepatitis B-Related Liver Diseases

ObjectiveInterleukin-28B is also named IFN-λ3, which belongs to the type Ⅲ IFN family.It is a kind of anti-hepatitis virus infection, and also exhibits anti-tumor activity.Except environmental and viral infection,host genetic immune background is also closely linked with the development of chronic hepatitis B virus(CHB),Liver cirrhosis(LC) and hepatocellular carcinoma(HCC).Previous studies had focused on the association of Interleukin-28B polymorphisms and liver diseases,but lacked of systematic research.In fact, it is a continuous process from hepatitis B virus infection to LC and HCC,and in some conditions,CHB,LC and HCC may overlap.We detected the polymorphisms of IL-28B rs 12979860 and rs8099917 to systematically explore the association between IL-28B polymorphisms with CHB, LC and HCC genetic susceptibility, meanwhile get the distribution of rs 12979860 and rs8099917 genotypes in Guangxi,which would provide new genetic targets and ideas for the prevention and individualized treatment of CHB, LC, HCC in Guangxi population.Methods1.Subjects:A total of 164 cases from physical examination was randomly selected for the healthy controls.The case group were 154 CHB patients,108 LC patients and 184 HCC patients in this case-control study.2.Genotype methods:Genomic DNA was extracted by the phenol-chloroform method from the anticoagulant blood of every objects.And the rs 12979860 and rs 8099917 gene polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).DNA direct sequencing method were used to confirm the accuracy of genotype at the same time.3.Data analysis:After counting the genotype and allele frequency,we performed chi-square test to examine the differences in controls and cases.Hardy-Weinberg equilibrium was tested to compare the observed genotype frequencies with the expected genotype frequencies among the subjects.SPSS16.0 sortware was used in all data analysis.Results1.All results in each site were not out of Hardy-Weinberg equilibrium(HWE) test (P>0.05),so each sample had good representativeness and comparability.2.We tested CC, CT and TT genotypes in the rs 12979860 in which genotype CC accounting for more than 79.00%, while the TT was least in Guangxi.Three genotypes included TT, TG and GG were found in the rs8099917, in which the genotype TT accounting for more than 86.00%,while the genotype GG was least in Guangxi.3.The distribution of genotypes and alleles:(1)The difference between the case groups and the control group in each genotype and allele in rs 12979860 was statistically significant(P<0.05).(2)The difference between the case groups and the control group in each genotype and allele in rs8099917 was not statistically significant(P>0.05).4.Gender distribution:(1)In the male population,the difference between the HCC group and the control group in each genotype and allele in rs 12979860 was statistically significant(P<0.05).(2)In the male population,the difference between the LC group and the control group in each genotype and allele in rs 12979860 was statistically significant(P<0.05).(3)In the female population,the difference between the case groups and the control group in each genotype and allele in rs12979860 and rs8099917 was not statistically significant(P>0.05).5.Age distribution:(1)Difference between CHB group and the control group was statistically significant(P<0.05) in each genotype and allele in rs 12979860 of the people under 40 years old.At the age of 40 to 60 years old, difference between HCC group and the control group was statistically significant(P<0.05) in each genotype and allele in rs12979860.(3)There was no statistically significant difference(P>0.05) in rs8099917 in all groups of all ages.6.National distribution:(1)In Han and Zhuang Chinese population, difference between HCC group and the control group was statistically significant(P<0.05) in each genotype and allele in rs12979860.(2)In Zhuang Chinese population, difference between LC group and the control group was statistically significant(P<0.05) in each genotype in rs8099917.Conclusions1.The mutant CC genotype frequency of rs 12979860 and the wild-type TT genotype of rs8099917 are the priority in Guangxi.2.The gene polymorphisms of rs 12979860 of interleukin-28B is associated with the susceptibility of liver diseases in Guangxi,and carrying T allele may be the one of the factors in the development of liver cancer,particularly reflected in the male population and under the 60-year-old people.3.The gene polymorphisms of rs8099917 of interleukin-28B is not associated with the susceptibility of liver diseases in Guangxi.The study may be affected by the limited sample size, while the expansile sample size being needed in the further research.