Genotype Distribution And Sequence Mutation Of Hepatitis B Virus In China

Hepatitis B remains the biggest public health challenge of china,as well as theworld.The WHO(World Health Organization)estimates that there are currently 400million individuals worldwide who are chronically infected with HBV,of whom 25%will die of chronic liver disease or hepatocellular carcinoma.The distribution ofgenotype of HBV is geographical.And the genotype of HBV closely relates with thedisease's control and prevention,with the disease's prognosis and with the antiviraltherapeutics.The mutation of HBV also associated with the vaccination and thedevelopment of the disease.So the study of HBV genotype and mutation can providethe basical characteristic of the HBV sequence and variation in china,which is thebasis of making the disease control's strategies and guiding the clinical therapeutics.The sera of the study are corned from 12 province of china.The HBsAg,HBcAg,HBeAg of the sera have been detected.The HbsAg positive is randomly selected toamplify the S gene by PCR.The genotype,sub-genotype and serotype aredeterminated by phylogenetic tree analysis with the standard genotype sequence of GeneBank,and the feature of distribution of the genotype is analysized.As the same times,theHBV C region is sequenced.The sera of non-concidenced genotype which made by Sand C region are selected.The full-length genome of HBV is amplified.In order toinvestigate the evolution of the sequence of HBV and the sequence mutationinfluenced by HBV vaccination.The HBsAg positive sera of 1992 and 2005 yearcollected from Hebei,Henan,Hunan and Guangxi province children.The children of1992 and 2005 groups are all under 18 years.The sequence of 1992 and 2005 groupsare amplified,and the mutation in"a"determinant of S antigen and the Large S geneare detected and compared between 1992 and 2005 groups'children.Meanwhile,theHBV large S sequence in the sera which come from adult of 1992 and 2005 areamplified,and the mutation in"a"determinant of S antigen is compared.Themutation in the C region is also detected by sequencing and analysized.And the study acquires 913 sequences eventually.The result of the studydemonstrate that the A～D genotype have been detected in china.And the B and C arethe major genotypes.In the northern china,genotype C is majority.Contrastly,in thesouthern china,the genotype B is majority.And genotype D mainly distribute in thewestern china.The dominant sub-genotype of B is B2,and the dominantsub-genotypes of C are C1 and C2.C3 and C5 sub-genotype are detected in Guangxi province.The ayr,ayw,adr and adw serotype have been detected in china.And theadr and adw are the major serotypes.The genotype has closely relationship with theserotype.The C genotype with adr serotype,the B and A genotype with adw and Dgenotype with ayw have the relationship.And the ratio of HBeAg of the personinfected by C genotype is higher than the one infected by B genotype.There is nogeographical feature of the distribution of mutant ratio of HBV a determinant.Thetotal mutant percentage of the HBV a determinant is 12.36%.In Heilongjiang andHenan provinces about 2-3% sequence is non-coincidence genotyped by S and C gene.The full-length genomes are sequenced.And an aberrant C/A recombinant HBVsequence is amplified and sequenced successfully.It is the first time being detected inchina.As to the mutation of sequence,the mutant ratio of HBV a determinant of the 2005children group is 14.93% that is higher than the 1992 children group which is 5.8%,the result have the stastically meaning.Especially,the mutant percentage in 145 acidamino site is 5.82% of the 2005 child group.The mutant percentage in 145 acid aminosite is 0.72% of the 1992 child group.2005 group is higher than the 1992 group.However,the 2005 the mutant ratio of HBV a determinant of the 2005 adult group is9.89% that is same with the 1992 children group which is 9.43%.The acid aminomutant ratio in S region of 1992 child group is 0.38mutation/sequence.But the acidamino mutant ratio in S region of 1992 child group is 0.62mutation/sequence.Thedifference between 1992 and 2005 groups has the statistical meaning.A1762T/G1764A two-site mutation and G1896A mutation are the mostly commonmutations in the HBV C gene region.The percentage of the two kind mutations is59.49% in Henan province and is 30.21% in Heilongjiang province.The chancehappened in C genotype is higher than in the B genotype.On a whole,the study demonstrates the characteristic of the HBV sequence indifferent region of china by the means of sequencing and trendance of HBV S genemutation by the comparision of 1992 and 2005 years.All of these can provide themeaningful reference to control and prevent the HB disease.