| ObjectiveInvestigating polymorphism of interleukin 28 B (IL-28B) gene rs-8099917 and rs-12979860. This study aimed at investigating whether these two SNP polymorphism of IL-28B gene are related to the response to HBeAg(+) chronic hepatitis B (CHB)nucleost ideanalogue(NUCs) therapy. To analyz the relationship between polymorphism of these two SNP to gender,age,initial ALT level and pretreatment HBV-DNA level.Also to analyz the role of IL-28B gene rs-8099917 and rs-12979860 in pathogenesis and response to NUCs antiviral therapy in HBeAg(+) chronic hepatitis B patients.MethodsWe analyzed the response status of the 110 HBeAg(+)-CHB who accepted the NUCs antiviral therapy at 24 weeks,48 weeks and 96 weeks.Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and DNA sequencing were used to analyz the genotype polymorphism in IL-28B genotype.The antiviral responses of 110 patients to NUCs therapy were evaluated and compared by classifying them into three groups according to IL-28B genotype polymorphism of rs-8099917:TT,GTand GG genotype groups and classifying them into another three groups according to polymorphism of rs-12979860:TT,CTand CC genotype groups. We used fluorescent quantitative polymerase chain reaction (FQ-PCR) to detect serum HBV-DNA levels; virology markers detection using enzyme-linked immunosorbent adsorption method (ELISA) detection. Results1. The all patients genotypes of the rs-8099917 were T/G.They are:TT,GT and GG genotype.The highest frequency of the three genotypes is TT genotype(90.00%). The lowest frequency of the three genotypes is GG genotype (0.91%). The all patients genotypes of the rs-12979860 were T/C.They are:TT,CTand CC genotype. The highest frequency of the three genotypes is CC genotype (88.18%). The lowest frequency of the three genotypes is TT genotype (0.91%).2. No significant difference among the three genotype groups of rs-8099917 were found in terms of the distribution of age (P=0.430>0.05),initial ALT level (P=0.375>0.05),pretreatment HBV-DNA level (P=0.852>0.05).The distribution of gender has significantly different among the GG and the GT,TT genotype groups(P=0.000<0.05 and P=0.000< 0.05). Also no significant difference among the three genotype groups of rs-12979860 were found in terms of the distribution of age (P=0.706>0.05),initial ALT level (P=0.900>0.05),pretreatment HBV-DNA level (P=0.864>0.05). Distribution of gender has significantly differentamong the TT and the CT,CC genotype groups (P=0.000<0.05 and P=0.000<0.05).3. Untill 24 weeks, the ALT normalization rates among the rs-8099917 TT,GT and GG genotype groups were 70.71%,60.00%and 100%. The rates among the rs-8099917 three genotype groups were not signiicantly different (P=0.629>0.05). The ALT normalization rates among the rs-12979860 CC,CTand TT genotype groups wert71.13%,58.33% and 100%. Also, the ALT normalization rates among the rs-12979860 three genotype groups were not significantly different (P=0.531>0.05).4. Untill 48 weeks, the rates of HBV-DNA undetectable and the frequencies of partial virologic response among the rs-8099917 GG,GT and TT genotype groups were 0%,70% and 63.63%.The rates among the rs-8099917 three genotype groups were not signiicantly different (P=0.382>0.05).The rates of HBV-DNA undetectable and the frequencies of partial virologic response among the rs-12979860 CC,CTand TT genotype groups were 59.79%,66.67% and 0%. The rates among the rs-12979860 three genotype groups were not signiicantly different (P=0.422>0.05) also. 5. Untill the 96 weeks, the rs-8099917 GG. GT and TT genotype groups achieved HBeAg seroconversion rate were 0%,60% and 47.47%.The HBeAg seroconversion rate among the rs-8099917 three genotype groups were not signiicantly different (P=0.653>0.05). Rs-12979860 CC,CTand TT genotype groups achieved HBeAg seroconversion rate were 46.39%,66.67% and 0%. No signiicant difference were found in the rs-12979860 three genotype groups (P=0.702>0.05).6. The HBeAg seroconversion of the 96 weeks among the combination groups of rs-8099917GT,TT genotypes and rs-1297860CT,CC genotypes (fuor combination groups:rs-8099917GT/rs-1297860CT groups,rs-8099917 GT/rs-1297860CC groups,rs-8099917TT/rs-1297860CT groups and rs-8099917 TT/rs-1297860CC groups) were not signiicantly different (P>0.05).Conclusion1. The all patients genotypes of the rs-8099917 were -T/-G.They are:TT,GT and GG genotype, the highest frequencies of the three genotypes is TT genotype and the lowest is GG genotype. The all patients genotypes of the rs-12979860 were-T/-C.They are:TT,CT and CC genotype, the highest frequencies of the three genotypes is CC genotype and the lowest is TT genotype.2. No significant difference among the three genotype groups of rs-8099917 and the three genotype groups of rs-12979860 were found in terms of the distribution of age,initial ALT level and pretreatment HBV-DNA level.The distribution of gender had significantly different among the rs-8099917 GG and the GT,TT genotype groups, also the rs-12979860 TT and the CT,CC genotype groups. Aboat the rs-8099917 GT,TT genotype groups, the male has a high proportion, but the GG genotype group is female; Aboat the rs-12979860 CT,CC genotype groups, the male has a high proportion, but the TT genotype group is female.3. The rs-8099917 and rs-12979860 genotype polymorphism of IL-28B were not associated with the antivirul response of NUCs to patients with HBeAg(+) chronic hepatitis B at the 24 weeks (the ALT normalization rate),48 weeks(the rate of HBV-DNA undetectable) and 96 weeks (HBeAg seroconversion rate) time-points. Also the combination groups of rs-8099917 GT,TT genotypes and rs-1297860 CT,CC genotypes were not associated with the HBeAg seroconversion at the 96 weeks time point.
|
PDF Full Text Request