Research Of Gene Copy Number Variations Of Immune-related Factors Of Patients With Chronic HBV Infection Of Different Progression

BackgroudChronic hepatitis B infection presents a variety of disease spectrum. There is no consensus about the reason for individual being different progression after chronic hepatitis B infection. But research shows that immune response plays an important role in the process of virus removal of HBV infection and immune clearance of the virus also causes immune damage of liver tissue, in which the antiviral immune responses of T lymphocyte cells is closely related to the liver inflammation. The level of immune response is different in the hosts, so the genetic background of host antiviral immunity is an important impact on the disease progression of HBV infection. Present study shows that copy number variation (CNVs) can affect gene expression by gene dosage effect and structural changes, thus affecting the progress and susceptibility of the disease and so on. To study the gene copy number variation (CNVs) of T lymphocyte function–related immune factors in different groups of chronic HBV infection of different progression will help further clarify the role of the genetic background in chronic hepatitis B infection .ObjectivesTo study gene copy number of PDCD1, CD274, BCL2L11, IL7R of 88 cases of control group, chronic HBV carriers group, chronic severe hepatitis group, HCC group,using Kruskal-Waills H test and Rank transform analysis to analyze the differences of gene copy number of four genes between four groups,so as to study the relationship between the host genetic background and the chronic hepatitis B progression.Materials and MethodsObject88 cases of chronic HBV carriers group, chronic severe hepatitis group and HCC group were admitted patients or outpatients of the 8th People's Hospital of Guangzhou from June 2006 to December 2008 and the control group was main from the employment of Guangzhou 8th People's Hospitalincluding, the age of 20-60 years. All the cases were confirmed as the chronic hepatitis B according to guideline.Methods(1). Using Taqman real-time PCR measured to determine gene copy number of PDCD1, CD274, BCl2L11, IL7R of control group, chronic HBV carriers group, chronic severe hepatitis group and HCC group.(2). Using Kruskal-Waills H test and Rank transform to analysis the differences of gene copy number of four genes between four groups.Results1. The gene copy number PDCD1 among the four groups were significantly different (P<0.05 [Kruskal-Waills H test ]). HCC group was significantly lower than the other three groups (P<0.0167 [Rank transformation analysis]), chronic HBV carriers group is higher than the control group, but the difference was not significant (P>0.0167 [Rank transform analysis]). The difference between the carriers group and chronic severe hepatitis group was not significant (P>0.0167 [Rank transformation analysis]).2. The gene copy number CD274 among the four groups were significantly different (P<0.05 [Kruskal-Waills H test ]). HCC group was significantly lower than the carriers group and chronic severe hepatitis group (P<0.0167 [Rank transformation analysis]).HCC group was lower than the control group, but the difference was not significant (P>0.0167 [Rank transform analysis]).The carriers group and chronic severe hepatitis group was significantly higher than the control group (P<0.0167 [Rank transform analysis]). The difference between the carriers group and chronic severe hepatitis group was not significant (P> 0.0167 [Rank transform analysis]).3. The gene copy number BCL2l11 among the four groups were significantly different (P<0.05 [Kruskal-Waills H test]). HCC group was significantly lower than the other three groups (P<0.0167 [Rank transformation analysis]). The carriers group was significantly higher than the other three groups (P<0.0167 [Rank transformation analysis]).There is no significant differences between the chronic severe hepatitis group and the control group (P>0.0167 [Rank transformation analysis]). chronic severe hepatitis group was lower than the carriers group (P = 0.02 [Rank transformation analysis]).4. There is no significant differences among the four groups of IL7R (P<0.05 [Kruskal-Waills H test]).Conclusions1.PD-1, PD-L1, Bim ,the immune function related factors,whose gene copy number variation existed among the control group, chronic HBV carriers group, chronic severe hepatitis group and HCC goup.2.There was no significant difference between chronic HBV carriers group, chronic severe hepatitis group and control group of gene copy number of PDCD1.The gene copy number of CD274 in chronic HBV carriers group and chronic severe hepatitis group were higher than the control group. The gene copy number of BCL2L11 in chronic HBV carriers group was lower than the control group.3.Ther was no difference among the chronic hepatitis B infection groups of different progression of gene copy number IL7R.4.The gene copy number of PDCD1, CD274, BCL2L11 in HCC group were lower than the control group, which is inconsistent with the previous findings of its expression. So further study should be put in the genome of hepatoma cells. 5.The gene copy number variation of immune-related factors and was not fully consistent with the trend of the gene expression, and there was no significant CNVs between the chronic HBV carriers group and chronic severe hepatitis group. Therefore, the study of gene polymorphism being combined with gene transcription and protein expression can help to fully understand the impact of immune and genetic factors on the prognosis of chronic hepatitis.