Study On TRAIL Gene Polymorphism And Chronic Hepatitis B In Chinese Han Populations From Shandong Province

Background:The hepatitis B is induced by infection with HBV. It is the most popular and serious infectious disease in China. About 5-10% hepatitis B may be transformed to chronic heptatitis, even to hepatic cirrhosis or liver cancer. At present, many researchers are interested in the relationships between apoptotic factors and chronic hepatitis B.Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) was found and named by Wiley in 1995.TRAIL is located on the chromosome 3q26 in humans and is composed of five exons. It encodes approximately 1.77 kb mRNA and 32.5 KDa trans-membrane (type II) glycoprotein composed of 281 amino acid. TRAIL belongs to TNF-super family, and its structure is similar to other TNF family members. By bindding to its receptor, TRAIL can induce apoptosis or play other biological effects. It has been reported that levels of TRAIL expression is correlated with HBV DNA in human peripheral blood. The expression of TRAIL may participate in the hepatic injury induced by immune reaction. The secretion of sTRAIL can reflect the progression of the disease and hepatic damage. It has been found that the occurrence of chronic hepatitis B is related to polymorphisms of many apoptotic factors, but the relationship between chronic hepatitis B and TRAIL polymorphisms has never been evaluated in the literature .Objective:To explore the association of TRAIL polymorphism with chronic hepatitis B by observing the polymorphism and gene frequency of TRAIL gene at 1525G/A and 1595C/T of the 3'-UTR in Chinese Han nationalityMethods:This study followed a case-control design. The polymorphisms of TRAIL gene were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RPLP) methods in 187 patients of chronic hepatitis B and 142 healthy controls.Results:1. The alleles of TRAIL at 1525G/A and 1595C/T have achieved genetic equilibrium in normal individuals (x~2=0.917,P=0.632) and patients with chronic hepatitis B (x~2=1.207,P=0.547) .2. The genotype frequencies of TRAIL at 1525 and 1595 in all subjects were the same.3. There was no significant difference in genotype frequencies of TRAIL at two sites between the male and female individuals in normal controls.4. The SNPs of TRAIL gene at 1525G/A and 1595C/T sites have significant difference between the male and female subjects in chronic hepatitis B group. The genotype frequencies of TRAIL at 1525GG/1595CC in female were significantly higher than those of males.5. There was significant difference in genotype frequencies at 1525G/A and 1595C/T sites between the normal controls and chronic hepatitis B individuals with HBeAg positive (x~2=6.230 P=0.044) .But There was not significant difference in genotype frequencies for the two sites between the normal controls and chronic hepatitis B subjects with HBeAg negative (x~2=4.070 P=0.131) .6. There was significant difference in genotype frequencies of TRAIL at 1525G/A and 1595C/T sites between the normal control and chronic hepatitis B group. No significant difference was found in allele frequencies of TRAIL at 1525G/A and 1595C/T sites between the normal controls and chronic hepatitis B cases.Conclusion:In conclusion, there was no significant difference in genotype frequencies of TRAIL at 1525G/A and 1595C/T sites between the male and female individuals in normal controls. While genotype frequencies of TRAIL at 1525G/A and 1595C/T sites showed significant difference between the male and female in patients with chronic hepatitis B.Significant difference was also found in genotype frequencies of TRAIL at the same sites between the normal controls and chronic hepatitis B cases with HBeAg positive. There was significant difference in SNPs of TRAIL at 1525G/A and 1595C/T sites between the normal controls and chronic hepatitis B cases,which indicated that TRAIL was related to susceptibility to hepatitis B. Background:The hepatitis B is induced by infection with HBV. It is the most popular and serious infectious disease in China. About 5-10% hepatitis B may be transformed to chronic heptatitis,even to hepatic cirrhosis or liver cancer. This change is related with many factors,such as age, immunity, drinking, infenction or drugs. It is found that morbidity of chronic heptatitis B in male is higher than that of female. There is no any evidence as to whether sex hormone makes a contribution to the development of chronic heptatitis B. Data showed that serum testosterone level of liver cancer patients with positive HBsAg was significantly higher than that of HBsAg-negative patients. In order to clarify the relationship between the level of testosterone and chronic heptatitis B,we detected the level of testosterone of 65 cases of chronic hepatitis B patients and 35 cases of normal control by Electrochemiluminescence. In order to evaluate the funtion of testosterone in the chronic heptatitis B,we analysed the relation between the level of testosterone and other biochemical parameters. The present study can provide a new method to prevent, diagnose and treat the chronic heptatitis B.ObjectiveTo investigate the correlation between testosterone and chronic hepatitis B incidence.MethodsTestosterone concentration in serum was detected in 65 chronic hepatitis B subjects and 35 healthy controls with an electrogenerated chemiluminescence method. Meanwhile, alanine aminotransferase(ALT), aspartate aminotransferase(AST), and gamma-glutamyl transpeptidase(GGT) were measured by International Federation of Clinical Chemistry(IFCC) recommended method respectively. Serum total bilirubin(TBIL) was detected by DCA method and alkaline phosphatase(ALP) was analyzed with AMP method. IgG, IgM or IgA were detected with immuno-turbidimetry method. HBV DNA level was monitored using real-time PCR.ResultsSerum testosterone concentration in chronic hepatitis B group was higher than that of healthy controls significantly (P<0.01) . Though the testosterone in HBeAg positive subjects was higher than that of HBeAg negative group,there was no significant difference (P>0.05) .In addition, ALT, AST, TBIL, GGT, ALP and IgG levels were higher than those of controls(P<0.05) .In chronic hepatitis B group, serum testosterone was not correlated with ALT,AST,TBIL,GGT,ALP and HBV DNA level. While testosterone was negatively correlated with IgG moderately.ConclusionSerum testosterone in chronic hepatitis B subjects is significant higher than healthy controls. So higher testosterone could be as one kind of susceptible factors of chronic hepatitis B.